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    MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy

    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Moderators:
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      MA12.01 - The Information Pathway to Randomisation: Patients Experience of the Mesothelioma and Radical Surgery (MARS2) Feasibility Trial

      10:30 - 10:35  |  Presenting Author(s): Angela Mary Tod  |  Author(s): Clare Warnock, Karen Lord, Liz Darlison

      • Abstract

      Background

      The Mesothelioma and Radical Surgery 2 (MARS 2) trial was established in the UK to evaluate the role of radical surgery, (Pleurectomy decortication), for the treatment of malignant pleural mesothelioma (MPM). It compares chemotherapy and surgery to chemotherapy alone. The feasibility trial included a nested qualitative sub-study. The sub study aimed to 1) understand the patient experience of MARS2 trial process and interventions and 2) Identify any information and support needs required by patients. We present here the results related to MARS2 participant’s information experiences and needs at the point of randomisation. Implications for information provision to enhance patient experience and overcome recruitment barriers1 within MPM trials are considered.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      41 in-depth longitudinal qualitative methods were used with 15 participants following randomisation. 9 participants received chemotherapy and surgery and 6 received chemotherapy alone. Interviews were conducted following randomisation, and at 6 and 12 months after the initial interviews. Participants randomised to surgery also had an interview after post-operative discharge. Data was collected between August 2015 and March 2017 and analysed using Framework analysis2

      4c3880bb027f159e801041b1021e88e8 Result

      The findings provide insight into the challenging context within which potential participants have to assimilate knowledge about a trial such as MARS2. Prior to hearing about the trial participants had encountered a diverse range of new and concerning experiences. These included worrying symptoms, diagnostic tests, investigations and the drainage of litres of fluid from the lung. They had to absorb an array of life-changing facts in a short time including that they had a rare incurable cancer with a poor prognosis; their illness was an occupational disease with legal and financial implications due to asbestos exposure. Participants attended their trial consultation soon after this challenging diagnostic information provision. The study reveals variations in understanding of the trial procedures, specifically decision-making regarding treatments, equipoise and the process of randomisation. Motivations for participating in the trial were identified along with preferences for information formats.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provides unique insight into the information pathway of MPM trail participants, from diagnosis to randomisation. Results suggest that improvements in presentation of trial information and the development of formats that can be tailored to individual needs and preferred ways of learning, many enhance experience of and recruitment to MPM trials. Working with patients to co-produce information that communicates challenging concepts effectively, (such as randomisation and equipoise), may be a useful approach to meeting this challenge.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.02 - Quality of Life Following Pleurectomy Decortication and Extrapleural Pneumonectomy for Pleural Malignant Mesothelioma

      10:35 - 10:40  |  Presenting Author(s): Wil Lieberman-Cribbin  |  Author(s): Andrea Wolf, Rebecca Schwartz, Raja Flores, Emanuela Taioli

      • Abstract

      Background

      Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). Questions remain as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy (P/D), is most effective and results in better outcomes for survival and involves fewer complications. A comprehensive review was conducted on MPM patients to assess differences in QoL following P/D and EPP.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Original research studies on QoL after mesothelioma surgery were identified through May 2018: 17 articles, 14 datasets encompassing 659 patients, were retrieved. Measures of lung function (FEV, FVC) and EORTC QLQ-C30 were compared 6 months following surgery with preoperative values.

      4c3880bb027f159e801041b1021e88e8 Result

      QoL data was available for 102 EPP patients and 432 P/D patients. Two studies directly compared QoL between the two techniques. While QoL was still compromised 6 months following surgery, P/D patients fared better than EPP patients across all QoL measures. Physical function, social function, global health and dyspnea were higher at follow-up for PD than for EPP, while other indicators such as pain and cough were similar. FEV and FVC were higher at follow-up for P/D compared to EPP, although only one study reported FEV and FVC following EPP.

      8eea62084ca7e541d918e823422bd82e Conclusion

      QoL is better for patients undergoing P/D compared to EPP for an extended period following surgery. Given the need for multimodality therapy and the aggressive nature of MPM, QoL outcomes should be strongly considered when choosing type of surgery for MPM.

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      MA12.03 - The Impact of Malignant Pleural Mesothelioma Histology on the Use of Surgery and Survival in a Population-Based Analysis

      10:40 - 10:45  |  Presenting Author(s): Chi-Fu Jeffrey Yang  |  Author(s): Nicholas Mayne, John Z Deng, Sarah J Commander, Thomas A. D'Amico, Mark Berry

      • Abstract

      Background

      Histologic subtype for malignant pleural mesothelioma (MPM) is known to be an important determinant of both treatment and survival. This study aimed to quantify the impact of MPM histology on the use of surgery and survival in a population-based analysis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Overall survival (OS) of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the National Cancer Database from 2004 to 2015 was evaluated using Kaplan-Meier survival analysis and multivariable Cox proportional hazard models.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 3,346 patients who met inclusion criteria, the histologic subtype was epithelioid in 2,326 patients (70%), biphasic in 482 patients (14%), and sarcomatoid in 538 patients (16%). Median survival was 16.2 [95% CI: 15.3 – 17.2] months in the epithelioid group, 10.9 [95% CI: 9.8 – 11.9] months in the biphasic group, and 5.3 [95% CI: 4.7 – 6.0] months in the sarcomatoid group (p<0.001). Cancer-directed surgery was utilized more often in epithelioid (31%, n=718) and biphasic patients (38%, n=181) compared to sarcomatoid patients (17%, n=91) (p<0.001). Among patients who underwent surgery, median survival was significantly better for epithelioid (22.6 [95% CI: 21.2 – 24.8] months) and biphasic (14.7 [95% CI: 12.6 – 17.3] months) histologies compared to sarcomatoid histology (7.7 [95% CI: 6.4 – 8.6] months) (p<0.001). Surgery was associated with better survival in multivariable analysis for epithelioid (HR 0.81; [95% CI: 0.72 – 0.93], p=0.002) and biphasic histologies (HR 0.69; [95% CI: 0.53 – 0.89], p=0.004), but not for sarcomatoid type mesothelioma (HR 0.87; [95% CI: 0.65 – 1.16, p=0.34). Further, the absolute difference in median survival between surgical and non-surgical therapy was more clinically significant for the epithelioid (22.6 vs 15.8 months; p <0.001 and biphasic (14.7 vs 10.4 months; p=0.001) patients compared to the sarcomatoid (7.7 vs 7.2 months; p=0.13).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this U.S. national analysis of patients with malignant pleural mesothelioma, surgery was most commonly used for epithelioid and biphasic histologies and was associated with a median survival of nearly 2 years and over 1 year, respectively. However, surgery was also used in almost 1 in 5 patients with sarcomatoid mesothelioma but was associated with a median survival of less than 8 months. These results suggest that the specific mesothelioma histology should be firmly established before surgery, and it is reasonable to aggressively treat select patients with epitheloid and biphasic mesothelioma with surgery, but that surgery should not be performed for most patients with sarcomatoid mesothelioma.

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      MA12.04 - Discussant - MA 12.01, MA 12.02, MA 12.03

      10:45 - 11:00  |  Presenting Author(s): Marc De Perrot

      • Abstract

      Abstract not provided

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      MA12.05 - Phase 1 Study of HSP90 Inhibitor Ganetespib with Pemetrexed and Cisplatin/Carboplatin Chemotherapy for Pleural Mesothelioma

      11:00 - 11:05  |  Presenting Author(s): Dean A Fennell  |  Author(s): Sarah Danson, Martin Forster, Denis Talbot, Penella Woll, Jennifer Child, Yenting Ngai, Laura Farrelly, Allan Hackshaw, Annabel Sharkey, Sara Busacca, Robert Hastings, Dan Barnes, Marianne Nicolson, Paul Taylor, Samreen Ahmed, Graham Mark Wheeler

      • Abstract

      Background

      There have been no new licenced therapies for mesothelioma in over a decade. Ganetespib is a small-molecule heat-shock protein 90 (Hsp90) inhibitor, with significant activity for down-regulating Hsp90 client protein levels. Prior evidence indicates efficacy for ganetespib in mesothelioma through critical survival pathways and synergies with antifolates and platinum chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a dose-escalation study of ganetespib in patients with pleural malignant mesothelioma and ECOG 0-1. Ganetespib was combined with standard pemetrexed/platinum therapy, using either cisplatin (GCisP), or carboplatin (GCarbP). Three ganetespib cohorts were: 100, 150 & 200mg/m2 given days 1 and 15, every 21 days. GCisP was evaluated using a 3+3 design. GCarbP followed an accelerated titration run-in using single patients, switching to a 3+3 design after one dose limiting toxicity (DLT). DLT was assessed during cycles 1-2 for GCisP and cycle 1 for GCarbP. Genomic instability was inferred by array-based analysis of somatic copy number.

      4c3880bb027f159e801041b1021e88e8 Result

      27 patients were treated (GCisP, n=16; GCarbP, n=11). Median age 66 (range 37-76), 6 PS-0/21 PS-1, and 25 male. Only 3 patients experienced DLTs, all at 200mg/m2: grade 3 nausea (GCisP, n=1; GCarbP, n=1); grade 2 infusion-related reaction (GCarbP, n=1). This dose was the maximum tolerated dose. Partial tumour response rate was 61% (14/23 evaluable patients); 7 patients had tumour burden reduction of >50% (Figure). PFS was better using 200mg/m2 versus 100mg/m2 (hazard ratio 0.32, 95%CI 0.11-0.95, p=0.04). One patient remains progression-free even after 37 months. Total loss of heterozygosity (LOH) was correlated with increased tumour burden (n=7, correlation=0.7, p=0.078).

      meso02abstract_bestresponse.png

      Figure. Best tumour response (% change in tumour burden from baseline)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ganetespib plus pemetrexed and platinum chemotherapy was well-tolerated in patients with pleural mesothelioma, with evidence of activity, particularly at the recommended dose of 200mg/m2. LOH correlated with poorer response to this triplet combination.

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      MA12.06 - STELLAR – Final Results of a Phase 2 Trial of TTFields with Chemotherapy for First-Line Treatment of Malignant Pleural Mesothelioma

      11:05 - 11:10  |  Presenting Author(s): Giovanni L Ceresoli  |  Author(s): Joachim G.J.V. Aerts, Jaroslaw Madrzak, Rafal Dziadziuszko, Rodryg Ramlau, Susana Cedres, Birgitta Hiddinga, Jan P Van Meerbeeck, Manlio Mencoboni, David Planchard, Antonio Chella, Lucio Crinò, Maciej Krzakowski, Federica Grosso

      • Abstract

      Background

      Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields have been shown to significantly extend survival of patients with glioblastoma when added to chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria included ECOG PS of 0-1, pathologically proven mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients were followed q3w (CT scan q6w) until disease progression. The primary endpoint was overall survival (OS) and secondary endpoints were response rate, progression free survival (PFS) and toxicity. This prospective, single arm study assumed an historical control with a median survival of 12.1 months (Vogelzang et al. 2003). The sample size provides 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.

      4c3880bb027f159e801041b1021e88e8 Result

      All 80 patients were enrolled between 2016 and 2017, with a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 56% smokers. 16% (13 patients) had metastatic disease and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy and 63% (50 patients) received carboplatin.

      Median OS was 18.2 months (95% CI 12.1-25.8) compared to 12.1 months in the historical control. Median PFS was 7.6 months (95% CI 6.7-8.6) compared to 5.7 months in the historical control. Partial responses were seen in 40.3% of patients and clinical benefit (PR+SD) was seen in 97.2% of patients. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Only 4 patients (5%) had grade 3 dermatitis. The following grade 3-4 systemic AEs were reported in >3% of patients: hematological AEs (15%) and fatigue (4%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The study met its primary endpoint of significant extension of survival for previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for the combination of TTFields to the thorax together with standard chemotherapy. These results support the addition of TTFields to standard chemotherapy in the treatment of first-line malignant pleural mesothelioma.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.07 - gC1qR Expression is Independently Prognostic for Survival Benefit Following Chemotherapy in Mesothelioma

      11:10 - 11:15  |  Presenting Author(s): Xiaoyu Li  |  Author(s): Takashi Eguchi, Rania G Aly, Navin Chintala, Kay See Tan, John Messinger, Marjorie G. Zauderer, Berhane Ghebrehiwet, Prasad S. Adusumilli, Ellinor I.B. Peerschke

      • Abstract

      Background

      Overexpression of gC1qR, a multicompartmental and multifunctional cellular protein, has been shown to promote chemotherapy-induced apoptosis in cancer cells, but compromise CD4 T-cell proliferation in viral infections. The goal of this study was to investigate the overexpression of gC1qR, and its prognostic association with chemotherapy and CD4 T-cell infiltration in malignant pleural mesothelioma (MPM).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays comprising 6 tumoral and 3 stromal cores from 265 patients with MPM (216 epitheloid, 26 biphasic, and 23sarcomatoid, 1989-2010) were investigated by immunohistochemistry for gC1qR expression (intensity and distribution by H-score, range 0-300), and CD4 T-cell infiltration. Overall survival (OS) was analyzed by the Kaplan-Meier method (high versus low gC1qR expression delineated by median score). Multi-variable analysis included clinical, pathological factors and stage (T, N).

      4c3880bb027f159e801041b1021e88e8 Result

      In comparison to benign and reactive mesothelial cells (median H-score 30), gC1qR is overexpressed (median H-score 155) in all histological types of MPMs (263/265, 99.2%). In epithelioid MPM patients – 1) among patients who received neoadjuvant chemotherapy (NAC), high gC1qR was associated with better median OS (25 vs.11 months, Fig1A), 2) among patients without NAC, high gC1qR was associated with better survival, survival benefit is pronounced in patients who received postoperative chemotherapy (median OS 38 vs.19 months, Fig1B), and 3) in multivariate analysis, high gC1qR was an independent factor for better OS. gC1qR expression did not correlate with CD4 T cell infiltration. However, among patients without NAC, high CD4+ T cell infiltration-high gC1qR expression was associated with better OS (26 vs 18,12, and11 months, Fig1C).

      gc1qr.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      gC1qR is overexpressed on MPM cells. MPM patients with high gC1qR expression have a significant survival benefit particularly following chemotherapy; or in the presence of high CD4 T-cell infiltration.

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      MA12.08 - Discussant - MA 12.05, MA 12.06, MA 12.07

      11:15 - 11:30  |  Presenting Author(s): Quincy Chu

      • Abstract

      Abstract not provided

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      MA12.09 - Preclinical Investigations of Folate Receptor Targeted Nanoparticles for Photodynamic Therapy of Malignant Pleural Mesothelioma

      11:30 - 11:35  |  Presenting Author(s): Tatsuya Kato  |  Author(s): Cheng S Jin, Hideki Ujiie, Kosuke Fujino, Daiyoon Lee, Hironobu Wada, Hsin-pei Hu, Licun Wu, Rober A Weersink, Juan Chen, Hiromi Kanno, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihiro Matsuno, Marc De Perrot, Brian C Wilson, Gang Zheng, Kazuhiro Yasufuku

      • Abstract

      Background

      Photodynamic therapy (PDT) following lung-sparing extended pleurectomy (EPD) for malignant pleural mesothelioma (MPM) has been investigated as a potential means to kill residual microscopic cells. High expression of folate receptor 1 (FOLR1) has been reported in MPM, and targeting the FOLR1 has been considered as a new potential strategy. We have developed FOLR1-targeting porphyrin-lipid nanoparticles (folate-porphysomes; FP) for PDT. The inhibition of survival pathways of activated epidermal growth factor (EGFR) also enhance the PDT efficacy. Here, we have combined these approaches by using FP based PDT together with an EGFR-tyrosine kinase inhibitor (EGFR-TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The frequency of FOLR1 and EGFR expression in MPM was analyzed using tissue microarrays. Confocal microscopy and a cell viability assay were performed to confirm the specificity of FOLR1-targeting cellular uptake and photocytotoxicity in vitro. In vivo fluorescence activation and the therapeutic efficacy were then examined. The effect of EGFR-TKI was assessed in vitro. The in vivo combined anti-tumor effect of EGFR-TKI and FP-PDT was then evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      FOLR1 and EGFR were expressed in 79 % and 89 % of the MPM samples, respectively. The intracellular uptake of FP corresponded well with FOLR1 expression. When MPM cells were incubated in FP and then irradiated at 671 nm, there was significant in vitro cell kill, which was inhibited in the presence of free folic acid, suggesting the specificity of FPs. FOLR1 targeting resulted in disassembly of the porphysomes and subsequent fluorescence activation in intrathoracic disseminated MPM tumors, as demonstrated by ex vivo tissue imaging. FP-PDT resulted in significant cellular damage and apoptosis in vivo. Furthermore, the combination of pre-treatment with EGFR-TKI plus FP-PDT showed further marked improvement of treatment responses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Folate-porphysome based PDT shows selective destruction of MPM cells based on FOLR1 targeting, and pre-treatment with EGFR-TKI further enhances the therapeutic response.

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      MA12.10 - Long-Term Impact of Radiotherapy Before Surgery for Mesothelioma on the Distribution of Memory T Cell Subsets

      11:35 - 11:40  |  Presenting Author(s): Junichi Murakami  |  Author(s): Licun Wu, Mikihiro Kohno, Mei-Lin Chan, Yidan Zhao, Zhihong Yun, Marc De Perrot

      • Abstract

      Background

      Postoperative recurrence remains one of the critical issues in treatments for mesothelioma. We previously reported that non-ablative, hypo-fractionated radiation before surgery generated an antigen-specific activation of the immune system and could provide an in situ vaccination with long-term protection against mesothelioma in our murine model. An effective immunological protection depends on memory T cell subset diversification. However, limited work has been done to address the distribution of memory T cell subsets and its effects on the immune system after radiotherapy followed by surgery for mesothelioma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      C57BL/6 mice bearing AE17-OVA tumor were treated with local radiotherapy (LRT). LRT 5Gy was delivered on days 10, 11 and 12. We performed radical tumor resection 7 days after LRT. The mice were re-challenged under the skin or into thoracic cavity with AE17-OVA 28 days after surgery and defined as immunological protective memory model if the tumors were completely rejected. Memory model received subcutaneous tumor inoculation once again (second rechallenge), samples were harvested on day 0, 3, 10. We investigated memory T cell subsets using flow cytometry. In addition, the harvested total splenocytes (effector) were co-cultured with CFSE-labeled AE17-OVA (target) for three days. Each of their cytotoxic potential was analyzed by evaluating a number of AE17-OVA and its early or late apoptosis.

      4c3880bb027f159e801041b1021e88e8 Result

      8 out of 10 mice completely rejected the subcutaneous tumor in mice treated with LRT and surgery after re-challenged. We observed significantly better survival in the memory model re-challenged into the thoracic cavity compared with no treatment mice. After subcutaneous tumor inoculation, central memory T cells (CD44[+]CD62L[+]KLRG1[-]) on day 0, effector memory T cells (CD44[+]CD62L[-]KLRG1[-]) and terminal effector T cells (CD44[+]CD62L[-]KLRG1[+]) on day 0, 3, 10 increased significantly in CD8[+] splenocytes of memory model compared with no treatment mice. This observation was also seen in draining and non-draining lymph nodes. The MFI of CFSE reflecting a number of AE17-OVA cells decreased, whereas the proportion of early (Annexin V[+]FVD[low]) or late (Annexin V[+]FVD[high]) apoptotic cells in CFSE[+] cells increased, depending on time passage and effector/target ratio after tumor inoculation in both memory model and naïve mice. However, during time passage, memory model always had a stronger cytotoxicity (even at Day 0) as compared to naïve mice.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data raise an important possibility that non-ablative, hypo-fractionated radiotherapy followed by surgery for mesothelioma contributes to the development and long-term maintenance of memory T cell subsets, which could remain poised to rapidly recall effector functions upon antigen re-exposure.

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      MA12.11 - Analysis of Angiogenic and Stromal Biomarkers in a Large Malignant Mesothelioma Cohort

      11:40 - 11:45  |  Presenting Author(s): Puey Ling Chia  |  Author(s): Prudence Russell, Khashayar Asadi, Carmel Murone, Marzena Walkiewicz, Ulf Eriksson, Andrew Scott, Thomas John

      • Abstract

      Background

      Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other mesothelium membranes. Agents targeting vascular endothelial growth factor (VEGF) receptor such as bevacizumab; and multi-kinase inhibitors like nintedanib [angiokinase inhibitor of VEGF, platelet-derived growth factor (PDGF) receptor and fibroblast growth factor receptor (FGFR)] have recently demonstrated efficacy in MM. In the setting of these new therapies, it is important to evaluate angiogenic and stromal markers in MM to assess their associated prognostic implications.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays (TMAs) were created from formalin-fixed, paraffin-embedded tissue samples obtained from 326 patients who underwent surgical resection or biopsy for MM between 1988 and 2014. PDGF-CC, FGFR-1, VEGF and CD31 expression were analysed by immunohistochemical (IHC) staining. The H-score method assigned a score of 0–300 to each sample, based on the percentage of cells stained at different intensities. The discriminatory threshold was set for each IHC stain (usually the median score) and samples were classified as low (below median) or high expression (above median). CD31 was evaluated via Chalkley’s method to evaluate microvessel density. We evaluated the association between expression of the biomarkers, clinicopathological factors and outcomes, in patients with MM.

      4c3880bb027f159e801041b1021e88e8 Result

      The histological subtypes comprised of 203/325 (62.5%) epithelioid; 72/325 (22.2%) biphasic; 42/325 (12.9%) sarcomatoid, or indeterminate. The median age was 67 (range 24-88) with Male: Female ratio of 266: 53.

      CD31 high (≥5) was seen in only 31/302 (10.3%) irrespective of histology (13/31 (42%) epithelioid; 10/31 (32%) sarcomatoid; 7/31 (23%) biphasic; 1/31 indeterminate).

      PDGF-CC high (≥150) was seen in 203/310 (65%) of all samples but was higher in epithelioid subtype [129/203 (64%)]. VEGF high (≥80) was seen in 219/322 (68%) of all MM with 143/209 (68%) of epithelioid histology.

      FGFR-1 high (≥40) was seen in 127/310 (41%) of all MM and 73/127 (57.5%) are of epithelioid histology.

      There was no association of VEGF and FGFR-1 IHC with survival nor differences between histological subtypes.

      There was a non-significant trend towards poorer survival in epithelioid tumours with increased PDGF-CC expression (OS 18.5 vs 13.2 months; HR 0.7928; 95%CI 0.5958 to 1.055, P=0.1110).

      High CD31 score was associated with significantly poorer survival (OS 12 vs 8.6 months; HR 0.48; 95%CI 0.2873 to 0.7941, P=0.0044). Of the 31 patients with high CD31 scores; 23/31 (74%) were also high for PDGF-CC and 20/31 (64%) with high VEGF scores.

      8eea62084ca7e541d918e823422bd82e Conclusion

      High PDGF-CC expression and CD31 scores are associated with poor survival in MM. Abrogating these pathways may have prognostic implications.

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      MA12.12 - Discussant - MA 12.09, MA 12.10, MA 12.11

      11:45 - 12:00  |  Presenting Author(s): Masaki Anraku

      • Abstract

      Abstract not provided

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    MA13 - Interventional Pulmonology

    • Type: Mini Oral Abstract Session
    • Track: Interventional Diagnostics/Pulmonology
    • Moderators:
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      MA13.01 - CT-Guided Transthoracic Needle Biopsy for Evaluation of PD-L1 Expression: Comparison of 22C3 and SP263 Assays

      10:30 - 10:35  |  Presenting Author(s): Kyongmin Sarah Beck  |  Author(s): Kyo Young Lee, Su Jin Hong

      • Abstract

      Background

      Although there are a few studies about concordance of different assays testing PD-L1 expression using surgical specimens, there hasn’t been any such concordance study using real-world biopsy specimens. However, many of the patients requiring immunotherapy and thus PD-L1 testing have unresectable lung cancer and have to rely on small biopsy results. Although phase 2 of Blueprint phase 2 does include core biopsy specimens, they are mixed with bronchial biopsy specimens and the absolute number is very small (n=20). We sought to evaluate the concordance of 22C3 and SP263 assays in a larger number CT-guided transthoracic needle biopsy (TNB) specimens.

      The purpose of this study was to assess the concordance of two commercially available diagnostic assays (22C3 and SP263) in evaluating programmed cell death ligand-1 (PD-L1) expression using specimens from CT-guided TNB in a routine clinical setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective analysis reviewed 202 non-small cell lung cancer (NSCLC) patients who underwent CT-guided TNB at our institution from April 2017 to February 2018. Among these, biopsy specimens tested with both 22C3 and SP263 assays were included for review. Concordance of PD-L1 expression levels determined by the two assays was assessed using intraclass correlation coefficient, and the agreement of dichotomized values at various cut-offs (1%, 25%, and 50%) were assessed using Cohen’s κ coefficient of agreement. Clinical characteristics and biopsy-related factors were also assessed for the association of concordance of PD-L1 expression detected by different assays

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 80 patients (M:F =47:33, mean age: 68.0 years) were included in the study. Concordance of PD-L1 expression levels was high (intraclass coefficient: 0.892) between 22C3 and SP263 assays. Agreements at cut-off levels of 1%, 25%, and 50% were also good, with κ values of 0.878, 0.698, and 0.790 respectively. Positive percent agreement was 93.2%, 100.0%, and 95.2% for agreements at 1%, 25%, and 50%. At multivariate analysis, the presence of emphysema was significantly related to discordant PD-L1 results (odds ratio: 0.059, p= 0.005).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a high concordance of PD-L1 expression evaluated with 22C3 and SP263 assays using CT-guided TNB specimens.

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      MA13.02 - PD-L1 Expression in EBUS-Guided Cytology Specimens of Non-Small Cell Lung Cancer is Not Affected by Type of Fixation: A Study of Matched Pairs

      10:35 - 10:40  |  Presenting Author(s): Alexander Haragan  |  Author(s): John Roy Gosney, Claire Chadwick, Tom Giles, Seamus Grundy, Victoria Tippett, Krishna Gumparthy, Andrew Wight, Hock Tan

      • Abstract

      Background

      No previous trials of immune modulators (IMs) to treat non-small cell lung cancer (NSCLC) have included ‘cytology’ specimens, dispersed cells aspirated from a tumour deposit or body cavity, for immunochemical assessment of PD-L1, a useful complementary or compulsory companion diagnostic test. This has led to the widely-held view that, in the absence of such ‘validation’, cytology specimens cannot be used to assess it. In many centres, endobronchial ultrasound (EBUS)-guided aspiration of the tumour or intra-thoracic lymph nodes is the preferred means of diagnosis and staging of NSCLC and such specimens account for the majority received for analysis. Failure to asses them has serious implications for appropriate management and might deny patients effective therapy. Much of this reluctance centres on the alleged effect of fixation in alcohol-based fixatives, the preferred method of cytopathologists, rather than formalin, the standard fixation medium for tissue specimens, on the expression of PD-L1 on the cell surface.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We compared expression of PD-L1 in 50 paired specimens of NSCLC, one fixed in an alcohol-based fixative and one in neutral-buffered formalin, taken from the same tumour deposit or lymph node during the same procedure. All were spun down and formed into a cell block before assessment for PD-L1 expression, which was by two appropriately-trained pathologists with extensive experience in its interpretation.

      4c3880bb027f159e801041b1021e88e8 Result

      In none of the 50 pairs studied was there any significant difference, qualitative or quantitative, in the pattern or extent of PD-L1 expression and, in the great majority, it was identical irrespective of fixation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is no evidence from this study that the use of alcohol-based fixatives has any effect on the expression of PD-L1 or its interpretation. Notwithstanding the general challenges in accurately assessing such expression, which are common to specimens of tissue as well as dispersed cells, pathologists should feel able to interpret cytology specimens with confidence and clinicians able to rely on the results.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.03 - Heterogeneity Analysis of EBUS-TBNA-Derived Specimens for Evaluation of PD-L1 Expression and Copy Number Alterations in Patients with NSCLC

      10:40 - 10:45  |  Presenting Author(s): Katsuhiro Yoshimura  |  Author(s): Yusuke Inoue, Kazuo Tsuchiya, Masato Karayama, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Koshi Yokomura, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura

      • Abstract

      Background

      Most patients with non-small cell lung cancer (NSCLC) are diagnosed at advanced stages and only small biopsy specimens are available for diagnosis in the majority of the patients. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful diagnostic modality and is becoming more relevant and essential procedure in the real-world clinical setting. However, it is poorly elucidated whether EBUS-TBNA-derived small specimens are suitable for evaluation of biomarkers such as PD-L1 alterations, because heterogeneity of PD-L1 expression limits the power as a guide to select patients who are likely to benefit from the PD-1/PD-L1 blockade therapy. In addition, PD-L1 copy number alterations (CNAs) have been proposed to potentially complement the predictive performance of PD-L1 expression. We here evaluated the utility of EBUS-TBNA-derived specimens in the assessment of PD-L1 protein and CNAs focusing on the heterogeneity with other biopsy/resected samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PD-L1 protein expression and CNAs in 71 EBUS-TBNA specimens of NSCLC were assessed. Corresponding 68 transbronchial biopsy (TBB) specimens, 13 resected primary tumors, and 6 resected metastases were comparatively analyzed. PD-L1 expression on tumor cells was assessed by immunohistochemistry (E1L3N). Positivity of ≥1% was used as the cut-off. PD-L1 CNAs were assessed with fluorescent in situ hybridization, and were classified into three categories: amplification, polysomy, and disomy. Concordance between EBUS-TBNA and other specimens were calculated.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age was 68 years (38-90 years). The cohort comprised 48 men (67.6%), 15 never-smokers (21.1%), and 39 adenocarcinomas (54.9%). The concordance of PD-L1 positivity between EBUS and the other specimens was moderate; κ=0.63 for EBUS vs TBB, κ=0.68 for EBUS vs the resected primary tumors, and κ=1.00 for EBUS vs the resected metastases. The concordance of PD-L1 CNA statuses was comparable with that of PD-L1 expression: κ=0.60 for EBUS vs TBB, and κ=0.74 for EBUS vs the resected primary tumors. When the PD-L1 copy number was assessed as a continuous variable, the correlation was also good/moderate: ρ=0.60 for EBUS vs TBB specimens, ρ=0.56 for EBUS vs the resected primary tumors, and ρ=0.80 for EBUS vs the resected metastases. Intratumorally, PD-L1 expression was significantly heterogeneous in whole sections of resected tumors, but PD-L1 CNAs was less heterogeneous than protein expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EBUS-TBNA-derived specimens can be used for the assessment of PD-L1 alterations including CNAs. The concordance of PD-L1 CNAs between EBUS-TBNA and TBB/resected specimens were comparable with that of PD-L1 expression. However, spatial heterogeneity should be taken into account to interpret both PD-L1 protein expression and CNAs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.04 - Discussant - MA 13.01, MA 13.02, MA 13.03

      10:45 - 11:00  |  Presenting Author(s): John Roy Gosney

      • Abstract

      Abstract not provided

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      MA13.05 - The Canada Lymph Node Sonographic Score: National Validation of a Sonographic Score to Determine Mediastinal Lymph Node Malignancy

      11:00 - 11:05  |  Presenting Author(s): Danielle Alexandria Hylton  |  Author(s): Julie Huang, Simon Turner, Daniel French, Chuck Wen, James Masters, Biniam Kidane, Jonathan David Spicer, Jenelle Taylor, Christian Finley, Yaron Shargall, Christine Fahim, Forough Farrokhyar, Kazuhiro Yasufuku, John Agzarian, Waël C. Hanna

      • Abstract

      Background

      At the time of endobronchial ultrasound (EBUS) staging for Non-Small Cell Lung Cancer (NSCLC), 6 ultrasonic criteria (Fig. 1) are used to assign a Lymph Node Sonographic Score (LNSS) that is predictive of malignancy. The LNSS has not gained widespread use due to lack of research demonstrating its validity and reliability among endoscopists. We hypothesized that LNSS correlates well with the probability of malignancy, potentially guiding decisions for lymph node (LN) biopsy.

      iaslc abstract lnss - figure 1_jpg.jpg

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a prospective study to assess the validity and reliability of the LNSS. The validation cohort comprised LN that were video-recorded from patients with NSCLC, and assigned a LNSS by an experienced endoscopist. Videos were then circulated to thoracic surgeons and interventional respirologists across Canada, who were asked to assign a score to each LN. All raters had demonstrated proficiency using our online education module, were blinded to staging information, and to each other. Each LN was scored by at least 3 independent raters. Pathological specimens were used as the gold standard for determination of malignancy. Regression, receiver operator curve (ROC), and Gwet’s AC1 analyses were used to test LNSS score performance, discriminatory capacity, and inter-rater reliability.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 300 LNs (18% malignant) from 140 patients were analyzed by 11 endoscopists across 7 Canadian centres. LNSS=0 was strongly predictive of benign LN (NPV= 95.69%, OR=49.2, p=0.001). LNSS ≤2.5 (OR=44, p=0.001) was determined as the cutoff for malignancy based on ROC analysis (c= 0.7757, 95%CI: 0.70281-0.84853). Inter-rater reliability for LNSS=0 was 0.8553 (95%CI:0.8158-0.8947, p=0.0001) and 0.46 for LNSS ≤2.5 (95%CI=0.3521-0.5012, p=0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The Canada LNSS shows excellent performance in identifying benign LN at the time of EBUS. A cutoff ≤2.5 has the potential to inform decision-making regarding biopsy or repeat biopsy/mediastinoscopy if the initial results are inconclusive. Further teaching and education are required to improve inter-rater reliability.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.06 - Endosonography with Lymph Nodes Sampling for Restaging the Mediastinum in Lung Cancer: A Systematic Review and Pooled-Data Analysis

      11:05 - 11:10  |  Presenting Author(s): Long Jiang  |  Author(s): Jun Liu, Wenlong Shao, Kassem Harris, Lonny Yarmus, Weizhe Huang, Jianxing He

      • Abstract

      Background

      Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for restaging the mediastinum after induction treatment in patients with lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Embase and PubMed databases were searched from conception to July 2017. Data from relevant studies were analyzed to assess sensitivity and specificity of EBUS-TBNA and EUS-FNA, and to fit the Hierarchical Summary Receiver-Operating Characteristic curves.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of nine studies consisting of 542 patients fulfilled the inclusion criteria. All patients were restaged by EBUS-TBNA, EUS-FNA or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of EBUS-TBNA and EUS-FNA were 66%(95% CI, 60%-72%) and 73%(95% CI, 52%-87%), respectively; and specificities were 100%(95% CI, 98%-100%) and 99%(95% CI, 90%-100%), respectively. The area under the HSROC curves(AUC) were 0.84(95% CI, 0.81-0.87) for EBUS-TBNA and 0.99(95% CI, 0.98-1) for EUS-FNA. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 69% (95% CI, 63%-75%), and specificity was 100% (95% CI, 97%-100%); and for patients who received chemoradiotherapy, the results seemed similar with sensitivity of 65% (95% CI, 50%-78%) and specificity of 100% (95% CI, 96%-100%).

      Variables

      No. of patients

      Pooled sensitivity (95% CI)

      Pooled specificity (95% CI)

      Negative Likelihood Ratio

      AUC

      In all mediastinal stations

      Overall

      543

      0.70 (0.65-0.75)

      1.00 (0.98-1.00)

      0.30 (0.21-0.43)

      0.93 (0.91-0.95)

      EBUS-TBNA

      424

      0.66 (0.60-0.72)

      1.00 (0.98-1.00)

      0.38 (0.26-0.54)

      0.84 (0.81-0.87)

      EUS-FNA

      226

      0.73 (0.52-0.87)

      0.99 (0.90-1.00)

      0.27 (0.14-0.53)

      0.99 (0.90-1.00)

      Combine

      106

      0.67 (0.53–0.79)

      0.96 (0.86–0.99)

      N/A

      0.81 (0.73–0.87)

      Subgroup analysis

      Chemo alone

      365

      0.69 (0.63-0.75)

      1.00 (0.97-1.00)

      0.35 (0.26-0.48)

      0.90 (0.88-0.94)

      Chemo radiotherapy

      130

      0.65 (0.50-0.78)

      1.00 (0.96-1.00)

      0.25 (0.06-1.02)

      0.97 (0.95-0.98)

      If negative Likelihood Ratio(LR-) is smaller: essentially a definite diagnosis when negative result.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer. For nondiagnostic results, a further more invasive approach should be thoroughly considered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.07 - Diagnostic Yield of N3 Hilar Staging by Endobronchial Ultrasonography (EBUS) in Lung Cancer

      11:10 - 11:15  |  Presenting Author(s): Antoni Rosell  |  Author(s): Jaume Bordas Martinez, Jose Luis Vercher Conejero, Guillermo Rodriguez Gonzalez, Cristina Martin Cabeza, Noelia Cubero De Frutos, Rosa-Maria Lopez Lisbona, Marta Diez Ferrer, Paula Notta, Roger Llatjos Sanuy, Jordi Dorca Sargatal

      • Abstract

      Background

      Systematic lung cancer staging with EBUS has proven to be equivalent to cervical mediastinoscopy. Nevertheless, in the daily practice it is common to explore and sample negative PET-CT hilar N3 lymph nodes (LN). This study aims to explore if there is enough evidence to support this clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective study from our database including 1,013 explorations over the last 5 years. Including criteria were patients with lung cancer staged by PET-CT and EBUS-TBNA. Mediastinal and hilar N3 LN with a short axis ≥ 5 mm were sampled with a 21G needle and assessed by rapid on site evaluation (ROSE). A single nuclear medicine expert reviewed blindly all PET-CT scans and determined the SUVmax of every LN. Those that were ≥ 5 SUVmax by PET-CT and/or ≥ 10mm in short axis by EBUS were considered abnormal.

      4c3880bb027f159e801041b1021e88e8 Result

      87 patients were included, of which 87% were male with a mean age of 66 years (SD 12.6). The final histopathology diagnoses were adenocarcinoma (46%), squamous cell carcinoma (39%) and other histology (14%). EBUS-TBNA was performed 30 days (SD 16.9) after PET-CT. None of the 61 normal hilar and normal mediastinum N3 LN, and none of the 7 normal N3 hilar LN with abnormal mediastinal LN (3 by PET-CT, 3 by EBUS and 1 for both) resulted positive for lung cancer. Of the 19 patients with abnormal N3 hilar LN (6 by PET-CT, 8 by EBUS and 6 for both) malignancy was found in 16.7% , 25% and 60% for both techniques, respectively.ryywawmo--450186-1-any.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      In absence of abnormal N3 hilar LN (PET: SUVmax<5; EBUS<10mm in short axis) it seems there is not enough evidence to sample them, regardless of N3 mediastinal status.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.08 - Discussant - MA 13.05, MA 13.06, MA 13.07

      11:15 - 11:30  |  Presenting Author(s): Nicole Bouchard

      • Abstract

      Abstract not provided

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      MA13.09 - Electromagnetic Navigation Bronchoscopy as an Integrated Approach to Aid in Diagnosis and Treatment of Pulmonary Lesions

      11:30 - 11:35  |  Presenting Author(s): Sandeep Khandhar  |  Author(s): Septimiu Murgu, Kyle Hogarth, William Krimsky, Javier Flandes, Otis Rickman, Momen Wahidi, Eric Sztejman, Philip Linden, Sadia Benzaquen, Sandeep Bansal, Erik Folch

      • Abstract

      Background

      Electromagnetic navigation bronchoscopy (ENB) is an image-guided localization approach to guide endoscopic tools to lung targets. In a single procedure, ENB aids in localizing lung lesions for biopsy or molecular profiling, fiducial placement for stereotactic body radiation therapy (SBRT), or dye marking for surgical resection. The multidisciplinary utility of ENB in a large, prospective, multicenter study is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      NAVIGATE (clinicaltrials.gov, NCT02410837) is a prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. From April 2015 to August 2016, 1,215 consecutive subjects were enrolled at 29 United States sites. Two-year follow-up is ongoing. A prespecified 1-year interim analysis is presented.

      4c3880bb027f159e801041b1021e88e8 Result

      ENB was used to aid in lung lesion biopsy (n=1157 subjects), fiducial placement (n=258), pleural dye marking (n=23), and/or lymph node biopsy (n=30). EBUS-guided lymph node staging was conducted in the same procedure in 448 subjects. The median lesion-to-pleura distance was 9mm. The median lesion size was 20mm; most were in the middle (30%) and peripheral (67%) thirds of the lung. Pathology results were malignant in 44.3% (484/1092) (54.1% Stage I, 11.1% Stage II, 17.0% Stage III, 17.7% Stage IV). Molecular testing was attempted in 30.7% (80/261) of adenocarcinoma or NSCLC-not-otherwise-specified cases overall and 57.9% (33/57) of Stage IIIB/IV cases. Tissue was adequate in 87.5% (70/80) of cases. EGFR mutations (14.7%) and ALK translocations (4%) were the most frequently observed genetic alterations. The ENB procedure was well-tolerated; 2.9% of subjects had procedure-related pneumothorax requiring hospitalization or intervention, lower than published rates for CT-guided core biopsy (25%) and CT-guided fine needle aspiration (19%). Subject-reported impact of ENB on daily activities was 0.9 out of 10 (0 = no impact).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In the largest prospective, multicenter study to date, ENB aided in lesion biopsy in the middle and periphery of the lung and tissue collection for molecular testing, with a very low morbidity. ENB facilitates a multidimensional approach to lung biopsy and mediastinal/hilar staging, offering the opportunity for multiple sites/tissues to be safely sampled in one anesthetic event.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.10 - Comparison of Pulmonary Nodule Location Between Preprocedural CT and Intra-Procedural Cone-Beam CT During Guided Bronchoscopy

      11:35 - 11:40  |  Presenting Author(s): Michael A. Pritchett

      • Abstract

      Background

      Electromagnetic navigation bronchoscopy relies on pre-procedural CT scans to create a virtual airway reconstruction that is used as a roadmap during bronchoscopy. These systems assume similarity between the position of the nodule during bronchoscopy and the pre-procedure CT scan. However, there are multiple factors that suggest that such assumption maybe inaccurate. These include differences in positioning, breathing motion, and the presence of atelectasis. In this study, we evaluated the lung nodule position between pre-procedural CT to interprocedural cone-beam CT (CBCT). In addition, we assessed the ability of a novel augmented endobronchial fluoroscopic guidance system (LungVision, Body Vision Medical Ltd, Israel) to overcome those differences in real-time.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was a prospective study of 21 patients with 23 peripheral pulmonary nodules. CT scans were imported into the planning software and the physician identified the nodule and navigation pathway. CBCT (Philips Allura Xper FD20) was used to scan the patient during the procedure. LungVision was used for real-time navigation and guidance during biopsy. The divergence in nodule location between the pre-procedural CT and the interprocedural CBCT was measured.

      4c3880bb027f159e801041b1021e88e8 Result

      The average patient age was 69 ± 8.6, median nodule size was 18mm with 74% of the nodules in the upper lobes. The average divergence of the nodule was 14.11 ± 9.9mm. Successful navigation was verified by CBCT in 91% of cases. Malignancy was diagnosed in 20 of 23 nodules for a diagnostic yield of 87%. No adverse events were reported.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study demonstrates a significant divergence in lesion location between pre-procedural CT and intra-procedural CBCT during guided bronchoscopy. This finding indicates that the change in nodule position between the CT and bronchoscopy could have a great impact on the diagnostic success of the procedure. This movement, sometimes greater than the size of the nodule itself, can lead to an inaccurate localization when relying solely on virtual bronchoscopic or electromagnetic navigation.

      CT to patient divergence does not appear to influence the accuracy of this novel navigation platform. The system is capable of tracking the nodules dynamically and can compensate for changes in patient positioning and respiratory motion during both navigation and biopsy which leads to a high diagnostic yield.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.11 - Photodynamic Therapy for Peripheral-Type Lung Cancer in a Multi-Center Clinical Trial

      11:40 - 11:45  |  Presenting Author(s): Jitsuo Usuda

      • Abstract

      Background

      Photodynanic therapy (PDT), is a treatment modality for many cancers, and uses a tumor-specific photosensitizer and laser irradiation. Recently, we have developed a new minimally invasive laser device using a 1.0 mm in diameter composite-type optical fiberscope (COF), which could transmit laser energy and images for observation in parallel.In this study, we aimed to develop a new endobronchial treatment for peripheral cancer using PDT and a COF, and we evaluated the feasibility of PDT using COF for peripheral lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This phase I study enrolled 3 patients with peripheral lung cancers (primary tumor< 20 mm, stage IA), which were definitively diagnosed by bronchoscopic modalities such as EBUS-GS and brocnhoscopic navigation system. We conducted irradiation using a diode laser (664 nm) and a COF 4 hours after the administration of NPe6 40 mg/m2. We evaluated the tumor lesions using EBUS, and then we introduced the COF into the peripheral lung cancer, and irradiated of red light 664 nm (120 mW, 50 J/cm2 or 100J/cm2). 

      4c3880bb027f159e801041b1021e88e8 Result

      We performed PDT for 3 patients with c-stage IA peripheral lung cancer, using a laser dose (120mW, 50J/cm2), and confirmed the feasibility of the dose. We escalated the laser dose and performed 4 patients using a laser dose (120mW, 100J/cm2).

      Seven patients met our criteria, and 5 cases were adenocarcinoma and 2 case squamous cell carcinoma. We were able to observe the cancer lesions at the peripheral lung by the COF, and feasibly irradiated. Two weeks and 3 months after NPe6-PDT, complications such as pneumonia and pneumothorax were not found, but one mildly found light skin-photosensitivity. Six months later, we found CR in 3 cases and SD in 4 cases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 1.0 mm COF was a very useful device of NPe6-PDT for peripheral lung cancers, and PDT was a feasible and non-invasive treatment for a peripheral type early lung cancer. In the future, for non-invasive adenocarcinoma such as AIS, NPe6-PDT will become a treatment modality.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.12 - Discussant - MA 13.09, MA 13.10, MA 13.11

      11:45 - 12:00  |  Presenting Author(s): Antoni Rosell

      • Abstract

      Abstract not provided

  • +

    MA14 - Survivorship, Socioeconomic and End-of-Life Considerations

    • Type: Mini Oral Abstract Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Moderators:
    • +

      MA14.01 - Life Sustaining Procedures, Palliative Care and Hospital Cost Trends in Dying Lung Cancer Patients in U.S. Hospitals: 2005-2014

      10:30 - 10:35  |  Presenting Author(s): Jinwook Hwang  |  Author(s): Ji won Yoo, Jay Shen, Sun Jung Kim, Sung Youn Chun

      • Abstract

      Background

      Little is known about the extent to which dying patients with lung cancer receive life-sustaining treatments and palliative care services at the end-of-life in U.S. hospitals. We examine hospital cost trends and the impact of palliative care utilization on the use of life-sustaining procedures in this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective nationwide cohort analysiswas performed using National Inpatient Sample (NIS) data from 2005 and 2014. We examined the receipt of both palliative care and life-sustaining procedures, defined as systemic procedures, local procedures, or surgeries using the International Classification of Diseases, 9th revision (ICD-9-CM).

      4c3880bb027f159e801041b1021e88e8 Result

      Figure 1.

      스크린샷 2018-05-05 05.44.27.png

      We used compound annual growth rates (CAGR) to determine temporal trends and multilevel multivariate regressions to identify factors associated with hospital cost. Among 77,394,755 hospitalizations, 120,144 patients were examined. During 10 years, the CAGR of hospital cost was 7.05% (p<.0001). In contrast, the CAGR of hospital lengths of stay was -3.77% (p<.0001). The CAGRs of palliative care was over ten percentage (13.30 %, p<.0001). However, the CAGRs of systemic procedures, local procedures, and surgeries were less than around one percentage (-1.13%, -1.07% and 1.42%, each p<.0001). Systemic procedures, local procedures and surgeries were associated with increased hospital cost and lengths of stay by 50.6%, 74.4%, 68.5%, and 7.4%, 50.6%, 4.6% respectively (each p<.001). Palliative care was associated with decreased hospital cost and length of stay by 28.6% and 4.6% (each, p<.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The volume of life-sustaining treatments is the biggest driver of cost increase although there is a cost-saving effect from greater palliative care utilization at the end-of-life in dying lung cancer patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.02 - Use and Impact of A Systematic Advanced Care Planning in Hospitalized Lung Cancer Patients: A Prospective Study.

      10:35 - 10:40  |  Presenting Author(s): Anne Claire Toffart  |  Author(s): Natacha Denis, Matteo Giaj Levra, Linda Sakhri, Michaël Duruisseaux, Julian Pinsolle, Léonie Ferrer, Denis Moro-Sibilot, Jean-François Timsit

      • Abstract

      Background

      End-of-life communication is crucial, particularly for cancer patients. In usual practice, advanced care planning discussions with the patients are uncommon and rarely documented. The aim of this study was to investigate the impact of advanced care planning on intensity of care in cases of organ failure in lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This prospective study was performed at the Grenoble University Hospital in France. Consecutive patients hospitalized in thoracic oncology unit between 01/28/2014 and 03/31/2016 were included and followed up to 12/31/2016. At each hospital admission, lung cancer patients benefited from advanced care planning. We defined 3 intensities of care: intensive care, maximal medical care and exclusive palliative care. The propositions of care could be modified during the hospitalization. Patients’ wishes should be received.

      4c3880bb027f159e801041b1021e88e8 Result

      Data of 715 hospitalizations corresponding to 473 patients were studied. Hundred fifty nine patients had a second hospitalization and 69 a third. At first admission, 247 (52%) patients had a performance status of 0 to 2, 186 (39%) were not yet treated for the cancer and 165 (35%) in progression. Main reasons of admission were an acute disease (n=208, 44%) and supportive care of cancer symptoms (n=167, 35%).

      During the three first admissions, 173 (25%) patients developed an organ failure. Among them, 56 (32%) had intensive care proposition, 104 (61%) maximal medical care, and 13 (7%) exclusive palliative care. Median time between admission and organ failure was 9 days [IQR 25%-75%, 3-13]. All patients benefited from intensity of care equal or lower than the proposed intensity of care. Among patients planed for intensive care, 17 (30%) patients received intensive care, 22 (39%) maximal medical care and 17 (30%) exclusive palliative care. Thirteen of the 39 patients not admitted in ICU despite organ failure and previous proposition of intensive care were considered too well by the oncologist. Patients’ wishes were recorded for 158 (91%) patients, and a discussion about end of life conditions was led with 116 (73%) patients or families.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In case of organ failure, an advanced care planning appears helpful to provide reasonable intensity of care. The proposition of care seems to be adapted to the patient’s general condition and cancer characteristics. 3/4 of the patients with an organ failure benefited from a discussion about end of life conditions.

      ClinicalTrials.gov Identifier: NCT02852629

      Funding from the publicly funded nonprofit organization Cancéropole Lyon Auvergne Rhône-Alpes (CLARA).

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.03 - Aggressiveness of Cares on the Month Before Death of Patients with Lung Cancer: A French National Database Survey

      10:40 - 10:45  |  Presenting Author(s): Olivier Bylicki  |  Author(s): Charlène Tournier, florence Canoui-Poitrine, Cecile Blein, Christos Chouaid

      • Abstract

      Background

      Prior studies have demonstrated that high-intensity end of life (EOL) cares improves neither survival nor quality of life for cancer patients. The National Quality Forum endorses markers of poor EOL care for cancer patients but there is little data’s concerning lung cancer patients (1). The aim of this study was to assess, the quality of management during the last month of life of lung cancer patients managed in France and factors associated EOL aggressiveness.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using a French hospital discharge database (PMSI, Programme de Médicalisation des Systèmes d’Information), all patients with lung cancer who died between January 1, 2010 and December 31, 2011 (cohort 1) and between January 1, 2015 and December 31, 2016 (cohort 2) were identified through the International Classification of Diseases 10th version (ICD-10). Aggressiveness of EOL cares was assessed by the following criteria’s 1) chemotherapy administrated within last 14 days of life (DOL); 2) > 1 hospitalization within 30 DOL; 3) ICU admission within 30 DOL; and 4) Palliative care < 3 days before death. Multivariate analysis was performed to identify individual determinants EOL aggressiveness.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 90,827 incident adult patients were identified (cohort 1: 43,862, cohort 2: 46,965): men: 74%, median age: 67 years], metastatic at diagnosis: 70%; 57% have at least one marker of aggressiveness of EOL cares (repeated hospitalizations: 49%, ICU admissions: 12%, chemotherapy within 14 DOL: 9%, palliative care < 3 days before death: 5%). A significant increase was observed between 2010/2011 and 2015/2016 for repeated hospitalizations (48% vs 51%, p<.001) and ICU admissions (11% vs 13%, p<.001); the two other markers have remained stable. In multivariate analysis of cohort 2, the risk of aggressiveness of care in EOL was increased by the presence of COPD (OR: 1.08, 95%CI: 1.02-1.14) and a management in an anti-cancer center (OR: 2.32,95%CI 2.05-2.61) while advanced age (OR: 0.51, 95%CI 0.47-0.55), female sex (OR: 0.86 95%CI: 0.82-0.90), malnutrition (OR: 0.72, 95%CI:0.68-0.76) were protective factors for EOL aggressiveness of cares.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite growing focus on providing appropriate EOL cares, in this analysis 57% of deceased lung cancer patients in France received aggressive EOL cares. Research must be undertaken to better identify patients at risk of aggressive EOL cares and to improve the quality of cares of last days of life these patients.

      1.McNiff KK, . Measuring supportive care in medical oncology practice: lessons learned from the quality oncology practice initiative. JCO 2008;

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.04 - Discussant - MA 14.01, MA 14.02, MA 14.03

      10:45 - 11:00  |  Presenting Author(s): Gouri Shankar Bhattacharyya

      • Abstract

      Abstract not provided

    • +

      MA14.05 - Social Isolation Increases Psychological Distress in Patients With NSCLC

      11:00 - 11:05  |  Presenting Author(s): Cheryl Ho  |  Author(s): Bonnie Leung, Jonn Wu, Janessa Laskin, Heather Rennie, Alan Bates

      • Abstract

      Background

      The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire is a validated screening tool used to identify the psychosocial needs of patients with cancer. The questionnaire assesses patients’ perceived social supports and identifies patients at risk for developing psychological distress. The study goal was to examine patients with NSCLC who reported risk factors for social isolation and their risk for developing psychological distress.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients with NSCLC referred to BC Cancer from 2011-2015 who completed a prospective PSSCAN-R questionnaire at the time of first visit were included in the study. Perceived social support questions include: if patients live alone, lost a life partner recently, have no help with IADLs, have no regular contact with friends and family or have no emotional support from others. Demographics were collected retrospectively. Chi-squared test and logistical regression were used to compare patient groups based on age, gender and perceived social support factors.

      4c3880bb027f159e801041b1021e88e8 Result

      The study cohort was comprised of 4428 patients who completed the PSSCAN-R questionnaire. Female 50%, patients ≥65 years 69%, live alone 29%, lost life partner 13%, no help with IADLs 9%, no regular contact 3% and no emotional support 5%.table1.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Female patients and patients younger than 65 are more at risk for developing moderate to severe anxiety and depression. Lack of perceived social support also contributes to the risk of developing psychological distress. In addition to developing gender and age-based resources for patients addressing their psychosocial needs, greater efforts in assessing patients’ perceived social supports and allocating community and institutional resources to isolated patients should also become an important part of the patients’ comprehensive and holistic care.

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      MA14.06 - Predictors of Financial Toxicity, an Under-Recognized Patient-Reported Outcome

      11:05 - 11:10  |  Presenting Author(s): Doreen Anuli Ezeife  |  Author(s): Josh Morganstein, Sally C Lau, Jennifer Law, Lisa Le, Penelope Bradbury, Geoffrey Liu, Frances A Shepherd, Natasha B Leighl

      • Abstract

      Background

      In contemporary cancer care, financial distress has been established as a clinically relevant patient-reported outcome (PRO) associated with worse mortality and quality of life, but remains under-recognized by health care providers. Our goal was to define predictors of patient financial toxicity (FT) in a public healthcare system.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced lung cancer were recruited from outpatient clinics at the Princess Margaret Cancer Centre (Toronto, Canada). FT was measured with the validated Comprehensive Score for Financial Toxicity (COST) instrument, an 11-item survey scored from 0-44 with lower scores reflecting worse financial well-being. Data on patient and treatment characteristics, total out-of-pocket costs (OOP) and extended insurance coverage (EIC) were collected. Associations between variables and COST score were evaluated using multivariable regression analyses.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 249 patients approached, 200 (80%) participated. Median age of the cohort was 65 years; 44% were male, 36% immigrants, 67% employed or on pension, with median OOP between $1000-5000 CAD. Median COST score was 21 (range 0-44). FT was associated with age, with patients <65 years reporting greater FT than older patients (COST 18 vs. 25; P<0.0001). Employed patients or those receiving pension income reported less FT than unemployed patients (22 vs. 19; P=0.01). Less FT occurred in patients with EIC compared to those without (23 vs. 19; P=0.03). Patients with higher OOP reported more FT (P<0.0001). Patients on clinical trials reported less FT than others (25 vs. 20; P=0.04). In multivariable linear regression, younger age was a predictor of higher FT, when adjusting for income, employment status, OOP and EIC (P<0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Age is a predictor of FT in the Canadian (Ontario) public healthcare system, with younger lung cancer patients reporting greater financial distress. This study highlights priority patient populations where FT should be routinely assessed and appropriate resources for support offered.

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      MA14.07 - The Impact of Socioeconomic Status and Geographic Location on Palliative Chemotherapy Uptake in Patients with Metastatic NSCLC 

      11:10 - 11:15  |  Presenting Author(s): Zamzam Salam Al-Hashami  |  Author(s): Bonnie Leung, Janessa Laskin, Jonn Wu, Heather Rennie, Alan Bates, Cheryl Ho

      • Abstract

      Background

      Socioeconomic status (SES) and geographic factors may impact patient treatment choices. Canada has a publically funded health care system and in BC, there are 35 community oncology network sites that delivery treatment in patients’ local communities. We studied the impact between SES and geographic location upon delivery of chemotherapy/survival in metastatic NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients with metastatic NSCLC referred to BC Cancer centres from 2011-2015, who completed a prospective Canadian Problem Checklist questionnaire at the time of their first visit and for which chemotherapy data was available were included in the study. The CPC assesses patient distress in 6 domains including practical aspects of cancer care. The Postal Code Conversion File Plus uses data from Statistics Canada 2011 census to determine population size and income quintiles. Baseline characteristics and chemotherapy treatments were collected retrospectively. Univariate analysis using the Chi-squared test and Fisher’s exact test were used for analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      1113 patients were included with median age of 69 years, 54% female and 77% were former/current smoker and 47% received palliative chemotherapy. Uptake of chemotherapy did not differ between lowest + mid-lowest 44%, middle 51% /mid-highest + highest 49% income quintiles (p=0.18). Chemotherapy use was also similar between patients reporting financial concerns 50% versus none 47% (p=0.51). Uptake of chemotherapy was lower in patients who lived in rural communities population<10 37% (P 0.00), 10K-1.5M 41%, >1.5 million 53% (p<0.001). Chemotherapy use was lower for patients with concerns about getting to appointments (39% vs 49%, p=0.008) or accommodations (33% vs 48%, p=0.012).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This dataset provide evidence that patients from rural communities were less likely to receive palliative chemotherapy treatment for metastatic NSCLC in BC despite the availability of multiple local community oncology services. SES did not appear to impact the proportion of patients treated, congruent with a government funded health care system. An in depth assessment of distances to local cancer services and treatment delivery is warranted to investigate these differences and their effect on mortality.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.08 - Discussant - MA 14.05, MA 14.06, MA 14.07

      11:15 - 11:30  |  Presenting Author(s): Christos Chouaid

      • Abstract

      Abstract not provided

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      MA14.09 - Mortality of Lung Cancer as a Second Primary Malignancy among Cancer Survivors: A Study of Surveillance, Epidemiology, and End Results Database

      11:30 - 11:35  |  Presenting Author(s): Lei Deng  |  Author(s): Huan Song, Zhengrui Xiao, Changchuan Jiang, Qian Wang, Haiying Cheng, Donghao Lu

      • Abstract

      Background

      Cancer survivors are at increased risk of developing a second primary malignancy, including lung cancer. However, the prognosis of lung cancer as a second primary malignancy (lung-2) remains largely unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Primary lung cancer patients diagnosed from 1988 to 2014 in the SEER program were included. Lung-2 was ascertained by a previous diagnosis of primary malignancy in SEER. Hazard ratios (HRs) of overall and lung cancer specific mortality were estimated among patients with lung-2 compared to lung-1.

      4c3880bb027f159e801041b1021e88e8 Result

      679,541(88.8%) and 85,758 (11.2%) patients were identified as lung-1 and lung-2, respectively. The median time from first primary malignancy to lung-2 diagnosis was 4.8 years. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 patients were at lower risk of lung cancer specific mortality in the first five years (HR 0.77, 95% CI 0.76 - 0.78 at < 1 year; HR 0.87, 95% CI 0.86 - 0.89 from 1 to < 5 years) but at higher risk thereafter. Patients with lung-2 were associated with reduced risk of overall mortality during the first year after diagnosis (HR 0.91, 95% CI 0.91 - 0.92), but with significantly increased risks thereafter.

      Table Hazard ratios (HRs) of overall and lung cancer specific mortality among patients with lung-2

      N (%) of patients

      From 0 to <1 year after diagnosis

      From 1 year to < 5 years after diagnosis

      From 5 years to 10 years of follow-up after diagnosis

      N (IR)

      HR (95% CI) *

      N (IR)

      HR (95% CI)*

      N (IR)

      HR (95% CI)*

      Overall mortality

      First primary lung cancer

      679,541

      383,208 (99.9)

      1.00

      135,513 (29.3)

      1.00

      16,821 (9.8)

      1.00

      Second primary lung cancer

      85,758

      44,288 (84.1)

      0.91 (0.91-0.92)

      20,073 (29.4)

      1.10 (1.08-1.12)

      3,133 (14.6)

      1.32 (1.27-1.37)

      Lung cancer specific mortality

      First primary lung cancer

      679,541

      325,633 (84.9)

      1.00

      111,348 (24.1)

      1.00

      8,147 (4.7)

      1.00

      Second primary lung cancer

      85,758

      31,247 (59.3)

      0.77 (0.76-0.78)

      12,485 (18.3)

      0.87 (0.86-0.89)

      1,158 (5.4)

      1.10 (1.03-1.17)

      N, number of deaths; IR, incidence rate per 100 person-years

      * HR was adjusted for age and calendar period at diagnosis, sex, race, cohabitation status, percentile of cost of living and high-school education in county of residence, tumor stage, histology, tumor grade, surgery, radiation therapy, and chemotherapy.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung-2 is associated with favorable lung cancer specific and overall survival within early period of diagnosis. Inferior overall survival afterwards cannot be attributed to aggressiveness of lung-2, highlighting the importance of managing first malignancy and comorbidities.

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      MA14.10 - QTc Interval-Prolonging Medications in Lung Cancer: Implications for Clinical Trial Eligibility and Routine Clinical Care

      11:35 - 11:40  |  Presenting Author(s): David E Gerber

      • Abstract

      Background

      Concomitant medication use, including agents that prolong the QTc interval, may exclude cancer patients from clinical trials. To estimate potential impact on accrual, we determined the prevalence of QTc-prolonging medication prescriptions in a national patient cohort.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We identified adult patients in the United States Veterans’ Affairs system diagnosed with lung cancer 2003-2016. QTc-interval prolonging medications and risk category were obtained from CredibleMeds®. We calculated prevalence of prescriptions for QTc-prolonging medications with known or possible risk of torsades de pointes (the most common criteria employed as trial exclusion criteria) in the 3 months up to and including date of cancer diagnosis. Rates across patient groups and time periods were compared using Chi-square test.

      4c3880bb027f159e801041b1021e88e8 Result

      280,068 patients were included in the study. Mean age was 70 years, 98% were male, and 72% were white. Overall, 29.7% were prescribed a QTc-prolonging medication. Patients receiving QTc-prolonging medications were marginally younger (mean age 68.9 years versus 70.9 years; P<0.001) and more likely to be black (14.1% versus 11%; P<0.001). The most commonly prescribed QTc-prolonging medications were antimicrobials (14.0%), psychiatric agents (10.2%), antiemetics (2.6%), and cardiovascular medications (1.7%). Seven percent of patients were prescribed two or more QTc-prolonging medications. Over the period of study, the rate of QTc-prolonging medication use increased 20% (25% in 2004 versus 31% in 2016; P<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      A substantial and growing proportion of individuals with lung cancer are prescribed QTc-prolonging medications. These prescriptions may limit eligibility for clinical trials and complicate the administration of standard cancer therapies. Given the prevalence of chronic and/or multiple QTc-prolonging medication prescriptions, it may be challenging to address this obstacle to trial enrollment simply through prescription substitution or discontinuation. Further research into the actual clinical risks and optimal management of QTc-prolonging medications in cancer populations is warranted.

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      MA14.11 - Factors Associated with Early Mortality in Non-Small Cell Lung Cancer Patients Following Systemic Anti-Cancer Treatment

      11:40 - 11:45  |  Presenting Author(s): Amanda Jane Williams Gibson  |  Author(s): Haocheng Li, Adrijana D'Silva, Roxana A. Tudor, Anifat A. Elegbede, Shannon Mary Otsuka, Winson Y Cheung, Gwyn Bebb

      • Abstract

      Background

      To determine a 30-day mortality rate benchmark and assess factors associated with early mortality of non-small cell lung cancer (NSCLC) patients following receipt of systemic anti-cancer therapies (SACT).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In a 10-year population-based analysis, NSCLC patients receiving SACT in 2005-2014, with or without other treatments, and captured in the Glans-Look Lung Cancer Database, which contains demographic, clinical, pathological, treatment and outcome data were reviewed. 30-day mortality after most recent SACT cycle was calculated, and end-of life (EOL) regimen changes in the last 14 days of life were identified. Univariate analysis and multivariable logistic regression were used to identify demographic, tumor or treatment-related factors that correlated with mortality risk.

      4c3880bb027f159e801041b1021e88e8 Result

      1044 eligible NSCLC patients receiving at least one cycle of SACT in 2005-2014 were identified. 51% were female, 62% adenocarcinoma, 79% current/former smokers, 83% advanced stage at diagnosis, and 77% receiving palliative-intent treatment. 233 (22.3%) deaths occurred ≤ 30 days following SACT receipt, and 32 (13.7%) EOL regimen changes identified. Risk of early mortality decreased for never-smokers and those receiving SACT between 2010-2014, and increased in association with male gender, advanced disease at diagnosis, palliative-intent treatment, and use of EGFR-targeting agents. No factors were associated with a decreased risk of EOL regimen change. (Table 1). The predominant SACT-modality among those experiencing 30-day mortality was EGFR-targeting agents (54%).
      abstract #12790 table.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings from a real-world population identify several factors which affect the risk of early mortality in NSCLC patients following SACT, and establish a 30-day mortality benchmark for Canadian NSCLC populations. Evolving SACT modalities may facilitate an increased use of SACT at EOL and associated early mortality; however, in this cohort, decreased early mortality risk in the 2010-2014 timeframe suggests concomitant evolution of decisions regarding EOL SACT and/or palliative and EOL care may be underway at our centre, but represents an area for ongoing investigation.

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      MA14.12 - Discussant - MA 14.09, MA 14.10, MA 14.11

      11:45 - 12:00  |  Presenting Author(s): Amanda Tufman

      • Abstract

      Abstract not provided

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    MS13 - Novel Mediators of Lung Cancer Metastasis

    • Type: Mini Symposium
    • Track: Biology
    • Moderators:
    • +

      MS13.01 - Liquid Biopsy-mediated Identification of Metastatic Variants

      10:30 - 10:45  |  Presenting Author(s): Philip Christopher Mack

      • Abstract

      Abstract not provided

    • +

      MS13.02 - Capicua Inactivation Drives Lung Cancer Metastasis

      10:45 - 11:00  |  Presenting Author(s): Trever G Bivona

      • Abstract

      Abstract not provided

    • +

      MS13.03 - Ubiquilin as a Novel Mediator of Lung Cancer Invasion and Metastasis

      11:00 - 11:15  |  Presenting Author(s): Levi J. Beverly

      • Abstract

      Abstract not provided

    • +

      MS13.04 - Tracking the Evolution of Non-Small-Cell Lung Cancer

      11:15 - 11:30  |  Presenting Author(s): Charles Swanton  |  Author(s):

      • Abstract

      Abstract not provided

    • +

      MS13.05 - Discussant

      11:30 - 11:45  |  Presenting Author(s): David Beer

      • Abstract

      Abstract not provided

    • +

      MS13.06 - Q&A

      11:45 - 12:00

      • Abstract

      Abstract not provided

  • +

    MS14 - IO in Early Stage NSCLC

    • Type: Mini Symposium
    • Track: Immunooncology
    • Moderators:
    • +

      MS14.01 - Basic Science Rationale of IO in Early Stage NSCLC?

      10:30 - 10:45  |  Presenting Author(s): Johan F. Vansteenkiste  |  Author(s): Christophe A. Dooms

      • Abstract

      Abstract not provided

    • +

      MS14.02 - Adjuvant / Neoadjuvant IO Therapy

      10:45 - 11:00  |  Presenting Author(s): Julie R. Brahmer

      • Abstract

      Abstract not provided

    • +

      MS14.03 - Concerns About IO for the Thoracic Surgeon?

      11:00 - 11:15  |  Presenting Author(s): Bernward Passlick

      • Abstract

      Abstract not provided

    • +

      MS14.04 - IO - New Standards in Stage III NSCLC

      11:15 - 11:30  |  Presenting Author(s): Rafal Dziadziuszko

      • Abstract

      Abstract not provided

    • +

      MS14.05 - Do Biomarkers used in Metastatic Setting Apply in Earlier Stages

      11:30 - 11:45  |  Presenting Author(s): Naiyer A Rizvi

      • Abstract

      Abstract not provided

    • +

      MS14.06 - Q&A

      11:45 - 12:00

      • Abstract

      Abstract not provided

  • +

    MS15 - Disruptive Technology and Lung Cancer Risk

    • Type: Mini Symposium
    • Track: Prevention and Tobacco Control
    • Moderators:
    • +

      MS15.01 - Just Water Vapor? Toxicology Perspectives on Electronic Cigarettes

      10:30 - 10:45  |  Presenting Author(s): Maciej Lukasz Goniewicz

      • Abstract

      Abstract not provided

    • +

      MS15.02 - PRO- Electronic Cigarettes: A Cessation Tool

      10:45 - 11:00  |  Presenting Author(s): K. Michael Cummings

      • Abstract

      Abstract not provided

    • +

      MS15.03 - CON- Electronic Cigarettes: Not Evidence Based Cessation

      11:00 - 11:15  |  Presenting Author(s): Alison Wallace

      • Abstract

      Abstract not provided

    • +

      MS15.04 - The Rise of Heat-Not Burn Tobacco in Japan: A “Hot” Issue for Tobacco Control

      11:15 - 11:30  |  Presenting Author(s): Junji Yoshida

      • Abstract

      Abstract not provided

    • +

      MS15.05 - Heat-Not-Burn Tobacco: Real Risk Reduction or Industry’s Next Promise

      11:30 - 11:45  |  Presenting Author(s): Carolyn Dresler

      • Abstract

      Abstract

      So, the question is: what are we to think about the products emerging from the global tobacco manufacterers that are being marketed in upper income countries? To be clear the topic is not about electronic nicoitne delivery systems (ENDS) that have been sweeping the world’s marketplaces - those arise from a multitude of mostly small companies. ENDS are an interesting topic that is quickly changing also - but, not the topic of this dissertation.

      Rather the topic for this paper will discuss the current market-disrupters which are the so-called ‘heat not burn’ cigarettes (HNB). The tobacco control community tends to call them ‘heated tobacco products’ (HTP), as some of them do come close to ‘burning’ (combusting) the tobacco, so, HTP is a more accurate, broad term for the category. The question to be addressed is whether they are less harmful than cigarettes or are they the usual ‘oversell’ or untrue marketing claims that have been the usual practice of the global tobacco manufacturers.

      A brief review: the global tobacco manufacturers are: Philip Morris, International. (PMI-Switzerland); British American Tobacco (BAT-UK); Imperial Tobacco (UK); Altria (USA) and Japan Tobacco International (JTI- Japan).(see: https://www.statista.com/statistics/259204/leading-10-tobacco-companies-worldwide-based-on-net-sales/). Altria is really just a spin-off from Philip Morris International who sells their products in the USA, including trying to do so for their HNB product (iQOS). Each of them have their own offerings in the HNB category: PMI/Altria is the current leader with iQOS, quipped as standing for: I quit ordinary smoking; BAT has ‘glo’; and Imperial has not embraced/marketed a HNB product but had thought to stay with their ENDS (blu) product. Reportedly, Imperial is considering getting their own HNB, as this category appears to be growing (commerically renumerative). JTI has PloomTECH.

      IQOS and glo use a lithium battery to heat compressed/powdered tobacco to around 300 Celsius which creates an aerosol for inhalation. PloomTech heats a liquid that has nicotine in it (closer to an ENDS)

      A recent paper by Farsalinos et, tested iQOS, an ENDS and a regular cigarette for emitted carbonyls, like formaldehyde and acrolein. (1) They found that iQOS emitted 82-98% less carbonyls compared to smoking 20 tobacco cigarettes. The ENDS emitted 92-99.8% less carbonyls. So, iQOS were better than cigarettes by alot, but the ENDS was better still.

      In a webpage hosted by RIVM (National Institute for Public Health and the Environment, misistry of Health, Welfare and Sport), their research to date is quoted as:

      “Heated tobacco products are newly available on the market. An example of such a product is the heatstick which is heated with an iQOS, a device that looks like an e-cigarette. Heating the heatstick leads to the formation of carcinogenic and other harmful substances. The use of heatsticks with the iQOS is harmful to health, but probably less harmful than smoking tobacco cigarettes. This is RIVM’s conclusion, based on its research into heated tobacco products (HTPs).”(2)

      In another recent paper from Japan, HTPs (iQOS, glo and Ploom TECH) were compared with ‘reference cigarettes’(research cigarettes that are well-defined and not for human consumption (as if any should ever be)). (3) Chemists interested in these findings should check out this paper. For the rest of us - it just demonstrates the tremendous variability in the products. Cigarettes deliver nicotine better than the other tested products, and iQOS does better than glo which does better than PloomTech. Since users are going for the nicotine, it seems that the order of preference will be cigarettes, iQOS, glo and PloomTech. However, the manufacturers are constantly changing their products, so they could be different next month. (This is the problem of unregulated products)

      Most of the published/available research is by the tobacco industry. For the hardy, there is a very large amount of scientific information from PMI on their iQOS submission to the USA FDA. (4) This is all publicly available information - and actually, a very interesting read. The question always remains when reviewing tobacco industry research - can it be verified?

      Overall, however, it does seem that heated tobacco products (or, ENDS) deliver lower levels of most toxicants to the human lung. Low enough to prevent disease is a different question. BUT, cigarettes kill more than half of the people who use them, cause a huge amount of morbidity and healthcare costs - and, are addictive. So, the question facing society - or, public health - is it possible or probable that if people who are already addicted to nicotine and using cigarettes switch (completely) to HTP products - would there be lower morbidity and mortality than we currently experience from cigarttes? No one knows the answer at present - and, we are unlikely to know for a few decades the real answer.

      However, are we horrified enough at the currently greater than 7 million deaths globally per year from cigarettes to radically alter our passionless inactivity and push, by regulation (and social pressure) for people to quit cigarettes. If they use HTPs (or ENDS) to quit the unacceptably deadly cigarettes, so be it. I don’t know how they could be worse than what we currently allow.

      {Disclaimer: I am still passionate about the standard tobacco control measures that are working in some countries, per the Framework Convention for Tobacco Control. I do not trust the global tobacco manufacturers that they are willing to help everyone in the world to quit cigarettes, particularly in low income countries, where these HTP products would be more expensive (unaffordable?) for their current customers. I believe the industry is still intersted in maintaining tobacco addiction - I want to ultimately reduce it as far as possible. First however, I want people who are nicotine addicted to stop dying from that addiction.}

      1. Farsalinos KE at al. Addiction 2019 June 19. doi: 10.1111/add 14365

      2. https://www.rivm.nl/en/Documents_and_publications/Common_and_Present/Newsmessages/2018/Addictive_nicotine_and_harmful_substances_also_present_in_heated_tobacco (accessed 6/29/2018)

      3. Uchiyama S. et al. Simple Determination of gaseous and particulate compounds generated from heated tobacco products. Chem. Res. Toxicol 2018.

      4. https://www.fda.gov/tobaccoproducts/labeling/marketingandadvertising/ucm546281.htm (accessed 6/29j/2018)

      e353dbe42c8654f33588d4da0b517469

    • +

      MS15.06 - Q&A

      11:45 - 12:00

      • Abstract

      Abstract not provided

  • +

    OA10 - Right Patient, Right Target & Right Drug - Novel Treatments and Research Partnerships

    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Moderators:
    • +

      OA10.01 - Patient Preferences for Tyrosine Kinase Inhibitor Treatments for EGFR Mutation Positive Metastatic NSCLC

      10:30 - 10:40  |  Presenting Author(s): John F.P. Bridges  |  Author(s): Marie De La Cruz, Melissa Pavilack, Emuella Flood, Ellen Janssen, Nabil Chehab, Ancilla W. Fernandes

      • Abstract

      Background

      EGFR mutation positive (EGFRm) NSCLC responds to EGFR-tyrosine kinase inhibitors (TKIs). First-, second-, and third-generation EGFR-TKI treatment attributes vary in efficacy, side effects, and dosing regimen. We used two different methods to explore treatment preferences among patients with EGFRm metastatic NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with EGFRm metastatic NSCLC were recruited in the US to participate in an online survey containing two complimentary preference elicitation methods. First, preferences were assessed through direct elicitation exercises where participants chose between competing treatment profiles. The first exercise compared two profiles with a large difference in progression-free survival (PFS) (6 vs 18 months). The second exercise compared two profiles with a smaller difference (10 vs 18 months). Both exercises compared the same side effect risks (0–1% vs 2–16% risk). Second, a discrete choice experiment (DCE) was used to assess preferences for variation in treatments in terms of PFS, severity of side effects (mild/moderate/severe), and mode of administration. These attributes and levels were varied based on a D-efficient design. Participants completed 10 DCE choice tasks where they saw pairs of hypothetical treatments with different attribute levels and selected their preferred treatment. A choice model was estimated using conditional logit regression.

      4c3880bb027f159e801041b1021e88e8 Result

      Between 10/2017 and 03/2018, 90 patients with EGFRm metastatic NSCLC were recruited and completed the survey: 42% female; 79% white; 76% taking first-line or second-line EGFR-TKIs at time of survey. Median time since diagnosis: 2.1 years (inter-quartile range: 1.1–2.7). In the direct elicitation exercise, participants opted for shorter PFS in exchange for more favorable side effects, but were less likely to do so for a large difference in PFS (52% of participants) vs a smaller difference (66%; p<0.001). Participants who chose shorter PFS when difference in PFS was large were more likely to be taking EGFR-TKIs (odds ratio: 21.4; 95% confidence interval: 2.24, 204.88). No relationship between choice and treatment characteristic was observed when difference in PFS was small. In the DCE, conditional logit regression indicated that to avoid severe levels of nausea/vomiting, diarrhea, rash, or fatigue, participants on average would accept reductions in PFS of 13, 11, 9, and 8 months, respectively. Participants would accept reduction in PFS of 7 months for oral treatment taken with/without food vs IV.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this online survey of patients with EGFRm metastatic NSCLC, some patients were willing to accept shorter PFS for a better safety profile and dosing convenience; however, PFS remained an important attribute in treatment choice.

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      OA10.02 - Oncogene-Driven Patient Groups: A New Era For Research Partnerships

      10:40 - 10:50  |  Presenting Author(s): Janet Freeman-Daily  |  Author(s): Ivy Elkins, Laura Greco, Marcia K Horn, Bonnie Addario, David LeDuc, Robert C. Doebele, Christine Lovly

      • Abstract

      Background

      Genomic alterations drive more than 60% of non-small cell lung cancer (NSCLC). About 20% of NSCLC cases (EGFR, ALK, ROS1, BRAF) will have an oncogenic driver that can be treated with approved targeted therapy drugs, and more have clinical trial options. In some cases, patients on targeted therapies will have years of good quality of life. However, targeted therapies do not cure, and these patients will eventually see their cancer progress. Patients and caregivers dealing with cancers driven by EGFR, ALK, ROS1 and Exon20 oncogenes have organized globally into online groups and are building partnerships that seek to provide support, increase awareness and education, accelerate and fund research, and improve access to effective diagnosis and treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Each patient-caregiver group forms using social media, patient blogs, websites, fliers, newsletters, and contacts with clinicians. Each has a private Facebook group or other network to inform and educate patients and caregivers of approved and experimental treatments, share common experiences, provide information and tips from expert clinicians and researchers, and enable real-life connections. Each group sets its own priorities such as creating websites, raising funds for research, donating tissue, developing studies of demographics and treatment sequences, and creating biorepositories with annotated specimens that will be made widely available. These projects are accomplished in patient-driven partnership with researchers, clinicians, advocacy groups, and industry. None of the patient-caregiver groups are corporations or other types of legal entities.

      4c3880bb027f159e801041b1021e88e8 Result

      The ROS1ders focus on ROS1+ cancers of all types and include over 275 members from 21 countries across 8 cancer types. They have partnered in two studies to create ROS1+ cancer models. ALK Positive focuses on ALK+ NSCLC and other cancers, and includes over 1000 members from 38 countries. They have raised nearly $400,000 for research and will announce two grants in May. Exon 20 Group focuses on EGFR and HER2 insertions in Exon 20, and includes 110 members from 19 countries. They created an Exon 20 molecular tumor board and awarded two grants. The EGFR Resisters focus on EGFR+ NSCLC and cancers that develop resistance to EGFR targeted therapies, and include over 450 members from 20 countries.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Oncogene-driven patient-caregiver groups are creating a new paradigm in cancer research and have demonstrated that their partnerships with advocacy organizations, clinicians, researchers and industry, combined with social media outreach, can increase available patient data, specimens, cancer models and research funding for geographically distributed, oncogene-driven cancer populations.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA10.03 - Discussant - OA 10.01, OA 10.02

      10:50 - 11:05  |  Presenting Author(s): Zofia Piotrowska

      • Abstract

      Abstract not provided

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      OA10.04 - Afatinib With or Without Cetuximab for EGFR-Mutant Non-Small Cell Lung Cancer: Safety and Efficacy Results from SWOG S1403

      11:05 - 11:15  |  Presenting Author(s): Sarah B Goldberg  |  Author(s): Mary W. Redman, Rogerio Lilenbaum, Katerina Politi, Thomas E. Stinchcombe, Leora Horn, Everett H. Chen, Sandeep Mashru, Scott N. Gettinger, Mary Ann Melnick, Jieling Miao, James Moon, Karen Kelly, David R. Gandara

      • Abstract

      Background

      Several EGFR tyrosine kinase inhibitors (TKIs) are used for the treatment of EGFR-mutant non-small cell lung cancer (NSCLC), however resistance inevitably develops. The combination of the irreversible ErbB family TKI afatinib and the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to first-line EGFR TKIs. To attempt to delay resistance, we conducted a randomized trial of afatinib plus cetuximab versus afatinib alone in treatment-naïve patients with advanced EGFR-mutant NSCLC (NCT02438722).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with previously-untreated EGFR-mutant NSCLC were randomized to afatinib 40mg PO daily plus cetuximab 500mg/m2 IV every 2 weeks or afatinib 40mg PO daily. The study was designed to accrue a total of 212 patients, comparing progression-free survival (PFS) between the arms at the 1-sided 0.025 level when 134 PFS events had been observed. Secondary objectives included comparison of overall survival (OS), time to treatment discontinuation (TTD), and toxicity. An interim analysis evaluating early stopping for futility occurred when at least 64 PFS events were reported.

      4c3880bb027f159e801041b1021e88e8 Result

      Between March 26, 2015 and April 23, 2018, 170 eligible patients were accrued: 86 to afatinib/cetuximab and 84 to afatinib. Median age was 66.4 years, 66% were female, 64% had an EGFR exon 19 deletion mutation and 36% had an L858R point mutation. With 109 events observed, there was no improvement in PFS with the combination compared to single-agent (HR 1.17, 95% CI 0.80-1.73, P = 0.42, median 10.6 months vs 13.1 months). OS was also not improved with the addition of cetuximab (HR 1.23, 95% CI 0.62-2.44, P = 0.55, median 26.9 months vs not reached). TTD was similar between the two groups (HR 0.95, 95% CI 0.64-1.39, P = 0.79, median 12.5 months vs 12.2 months). Grade > 3 treatment-related adverse events (AEs) were more common among patients treated with afatinib/cetuximab, and more patients in the combination arm required at least 1 dose reduction of afatinib (57% vs 26%). However, treatment discontinuations due to AEs were similar between the two groups (11.6% vs 10.7%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There was no difference in PFS, OS or TTD with the addition of cetuximab to afatinib for treatment-naïve patients with EGFR-mutant NSCLC. The trial was closed to accrual at the interim analysis having met the criteria for futility. Correlative analysis of tumor tissue and blood from patients is ongoing.

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      OA10.05 - An Open-Label, Multicenter, Phase II Single Arm Trial of Osimertinib in NSCLC Patients with Uncommon EGFR Mutation(KCSG-LU15-09)

      11:15 - 11:25  |  Presenting Author(s): Jang Ho Cho  |  Author(s): Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Keon Uk Park, Eun Joo Kang, Yoon Hee Choi, Ki Hwan Kim, Ho Jung, An An, Hyun Woo Lee, Myung-Ju Ahn

      • Abstract

      Background

      Approximately 10% of EGFR mutants harbor uncommon mutations, which represent a heterogeneous group of rare molecular alterations within exons 18-21 and the sensitivity to EGFR TKIs is variable. Osimertinib is a potent irreversible inhibitor of both sensitizing EGFR mutation and T790M. In preclinical data, osimertinib was found to be active against most uncommon EGFR mutants, apart from the exon 20 insertion variant. Here we present the efficacy and safety of osimertinib in patients with uncommon EGFR mutation positive NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with histologically confirmed metastatic or recurrent NSCLC with activating EGFR mutation other than exon 19 deletion, L858R, T790M and insertion in exon 20 were eligible. Patients received 80mg of osimertinib orally, once daily until progression or unacceptable toxicity. Response was assessed every 8 weeks by investigator. The trial was registered with ClinicalTrials.gov, number NCT03424759.

      4c3880bb027f159e801041b1021e88e8 Result

      Between Mar 2016 and Oct 2017, 35 patients were enrolled. Median age was 59, 63% male, 43% never smoker, 97% adenocarcinoma. 63% of patients were treated as first-line therapy. The mutations identified were G719A/C/D/S/X (19, 54.3%) followed by L861Q (9, 25.7%), S7681 (8, 22.9%), and others (3, 8.6%). The overall response rate was 50.0% (95% CI 32.8-67.2) and DCR was 88.9% (95% CI 78.1-99.7). Seven patients (77.8%) with L861Q mutation achieved partial response; 10/19 (52.6%) with G719A/C/D/S/X mutation; 3/8 (37.5%) with S768I mutation. At data cutoff (Apr, 2018), the median PFS was 8.2 months (95% CI 1.9- 14.4) and median duration of response was 9.8 months (95% CI 7.6-12.0). The most common adverse events were rash (n=11, 31.4%), anorexia (n=8, 22.9%), and diarrhea (n=7, 20.0%). Grade 3 or 4 AEs were reported in 8 of 35 patients (23%), but all of AEs were manageable.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib showed highly active in NSCLC patients harboring uncommon EGFR mutation with manageable safety profile, consistent with previous reports. Further analysis will be provided.

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      OA10.06 - A First-in-Human Phase 1 Trial of the EGFR-cMET Bispecific Antibody JNJ-61186372 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

      11:25 - 11:35  |  Presenting Author(s): Keunchil Park  |  Author(s): Myung-Ju Ahn, Se-Hoon Lee, Hye Ryun Kim, Min Hee Hong, Dawn Millington, Martin Curtis, Spyros Triantos, Sandra Chaplan, Nahor Haddish-Berhane, Roland Knoblauch, Zuleima Aguilar, Sylvie Laquerre, Matthew V. Lorenzi, Byoung Chul Cho

      • Abstract

      Background

      JNJ-61186372 (JNJ-372) is a bispecific antibody targeting both EGFR and cMET. In preclinical studies, JNJ-372 demonstrated efficacy in EGFR and cMET driven tumor xenograft models (including EGFR T790M and MET-amplified/HGF secretion), consistent with inhibition of ligand binding, receptor degradation, and ADCC activity. The goal of Part 1 of this study (reported here) was to assess the safety, pharmacokinetics (PK), and preliminary efficacy of JNJ-372 and to identify the recommended phase 2 dose(s) to be explored in Part 2.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with previously treated, advanced NSCLC were enrolled at two sites and treated with escalating doses of JNJ-372 administered IV weekly for the first 4-week cycle, then biweekly for each subsequent cycle. PK sampling was taken at multiple time points within cycle 1 and 2. Disease assessments were performed every 8 weeks. Tumors were characterized at baseline through next-generation sequencing of circulating tumor DNA (Guardant 360).

      4c3880bb027f159e801041b1021e88e8 Result

      25 patients were treated with JNJ-372 during dose escalation: 140mg (n=3), 350mg (n=3), 700mg (n=9), 1050mg (n=7), 1400mg (n=3). Median age was 63y, 48% were male, 100% were Asian, 84%/12%/4% had adenocarcinoma/squamous/other histology, and median prior therapies was 4. No dose-limiting toxicities were observed at any dose level tested. The most frequent treatment-emergent AEs were infusion-related reactions (76%), rash/acneiform dermatitis (40%), dyspnea (24%), paronychia (24%), pruritus (20%), fatigue (20%), and nausea (20%); incidence of peripheral edema (cMET-related toxicity) was 12%. Infusion-related reactions were grade ≤2 severity, observed primarily with the first dose. The worst severity of rash/acneiform dermatitis was grade 2 (16%). One treatment-related AE of grade ≥3 severity was reported (neutropenia grade 3, possibly related). JNJ-372 demonstrated linear PK at dose levels 350 mg and above with non-linear PK at lower concentrations, suggesting target-mediated drug disposition. Doses ≥700mg resulted in average steady-state concentrations at or above the preclinically established therapeutic target level. Preliminary evidence of efficacy (maximum change from baseline in sum of target lesion diameters) was observed in a patient with squamous cell carcinoma (-20%), a patient with wtEGFR adenocarcinoma (-20%), and 4 patients with EGFR-mutant adenocarcinoma (≥-30%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      JNJ-372 is a novel EGFR-cMET bispecific antibody. The manageable safety profile and preliminary evidence of clinical activity support active accrual of patients with previously treated EGFR-mutant NSCLC. The first recommended dose of 1050mg is being evaluated in Part 2.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA10.07 - Resistance Mechanisms of Osimertinib in Chinese Non-Small Cell Lung Cancer Patients: Analysis from AURA17 Trial

      11:35 - 11:45  |  Presenting Author(s): Caicun Zhou  |  Author(s): Min Hu, Xuehua Zhu, Yun Sun, Xuesong Lu, Jia Wang, Mengzhao Wang, Ying Cheng, Yuan Chen, Yanqiu Zhao, Yuan-Kai Shi, You Lu, Meiqi Shi, He-Long Zhang, Xiangning Huang, Zheng Wang, Zhijie Ding, Heyan Li, George Chen, Yi-Long Wu

      • Abstract

      Background

      Osimertinib is approved for metastatic NSCLC patients with EGFR T790M mutation after progression from TKI therapy. Despite impressive tumor responses, drug resistance usually develops. The resistance mechanisms of osimertinib are emerging but studies with large cohorts of Chinese patients and association with clinical outcomes are lacking. Here we report a biomarker study of osimertinib using plasma samples from 107 Chinese patients who had progressed by 24 months after LSFD (Oct. 2017) of AURA17 (NCT02442349), the 2nd-line pivotal trial in China.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Serial plasma cell-free DNA (cfDNA) were collected from baseline until progressive disease (PD) by investigator assessment. Capture-based 75-gene NGS panel with unique molecular index (UMI) system was used to identify resistance mechanisms to osimertinib by comparing paired cfDNA at baseline and PD. Droplet digital PCR (ddPCR) was used to dynamically monitor EGFR mutation changes (L858R, Ex19Del, T790M and C797S) during treatment course. Association of cfDNA biomarkers based on valid test results with objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) from DCO3 (Mar. 20, 2018) was analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      The 107 patients were with ORR of 68.2%, median PFS of 8.2 months, and median OS of 21.5 months. Eight-two had detectable EGFR sensitizing mutations (L858R or Ex19Del) in their PD cfDNA samples. Among them, 15 had acquired EGFR C797S, all in cis with T790M, and with no enrichment for L858R or Ex19Del (6 and 9, respectively). The median time of C797S detection from plasma was 2.8 (1.2-8.4) months prior to PD. EGFR L718Q, I744T, C775Y, G796S/D, T854I mutations, or amplification were found in 11 patients. Aberrations in bypass tracks including AKT2, ALK, DDR2, ERBB2/3, HRAS, JAK1/2, KRAS, MET, NTRK1, PIK3CA, RIT1, etc. were observed in 45 patients.

      Clearance of EGFR sensitizing mutations at weeks 3 of treatment was associated with favorable ORR (78.7% vs. 33.3%), PFS (9.6 vs. 4.0 months, p<0.001) and OS (21.5 vs. 11.7 months, p<0.001). Clearance of EGFR sensitizing mutations at weeks 6 of treatment was also associated with favorable ORR (80.0% vs. 36.8%) and PFS (8.3 vs. 4.2 months, p<0.001). Presence of T790M at PD was correlated with longer PFS (12.3 vs. 5.5 months, p<0.001) and OS (21.3 vs. 13.2 months, p=0.045). Acquired or enriched TP53 alterations at PD were associated with worse PFS (4.2 vs. 8.3 months, p=0.008).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study revealed diverse resistance mechanisms to osimertinib in Chinese NSCLC patients and urged for new drug discovery or combination strategies to overcome this clinical challenge.

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      OA10.08 - Discussant - OA 10.04, OA 10.05, OA 10.06, OA 10.07

      11:45 - 12:00  |  Presenting Author(s): Linda Coate

      • Abstract

      Abstract not provided

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    PC05 - Optimizing Clinical Trial Design in NSCLC

    • Type: Pro-Con Session
    • Track: Advanced NSCLC
    • Moderators:
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      PC05.00 - Introduction with Poll Questions

      10:30 - 10:35  |  Presenting Author(s): Pilar Garrido, Luis Ubillos

      • Abstract

      Abstract not provided

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      PC05.01 - Debate 1: Which is Most Important Efficacy Endpoint in First Line Trials in Advanced NSCLC PFS or OS - Point of View: PFS

      10:35 - 10:50  |  Presenting Author(s): Mary O’brien

      • Abstract

      Abstract not provided

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      PC05.02 - Debate 1: Which is Most Important Efficacy Endpoint in First Line Trials in Advanced NSCLC PFS or OS - Point of View: OS

      10:50 - 11:05  |  Presenting Author(s): Yu Shyr

      • Abstract

      Abstract not provided

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      PC05.03 - Discussion

      11:05 - 11:10

      • Abstract

      Abstract not provided

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      PC05.04 - Debate 2: Patient Reported Outcomes Should Be the Most Important Endpoint in Trials in the Palliative Setting - YES

      11:10 - 11:25  |  Presenting Author(s): Maurice Pérol

      • Abstract

      Abstract not provided

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      PC05.05 - Debate 2: Patient Reported Outcomes Should Be the Most Important Endpoint in Trials in the Palliative Setting - NO

      11:25 - 11:40  |  Presenting Author(s): Rathi N Pillai

      • Abstract

      Abstract not provided

    • +

      PC05.06 - Discussion

      11:40 - 11:45

      • Abstract

      Abstract not provided

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      PC05.07 - Let's Not Forget Chemo-Regret

      11:45 - 11:55  |  Presenting Author(s): Patricia J. Hollen

      • Abstract

      Abstract not provided

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      PC05.08 - Discussion

      11:55 - 12:00

      • Abstract

      Abstract not provided

  • +

    ISS14 - Symposium Supported by Novartis: Expert Perspectives on the Management of NSCLC in Clinical Practice: Are Novel Approaches Realistic? (Not IASLC CME Accredited)

    • Moderators:
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      Symposium Supported by Novartis: Expert Perspectives on the Management of NSCLC in Clinical Practice: Are Novel Approaches Realistic?

      12:00 - 13:30  |  Presenting Author(s): Daniel S.W. Tan, Scott A. Laurie, Laura Q Chow

      • Abstract

      Abstract not provided

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    EXH02 - Thermo Fisher Exhibit Showcase Session - The Way We Test Matters for Patient Outcomes (Not IASLC CME Accredited)

    • Type: Exhibit Showcase
    • Track:
    • Moderators:
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      EXH02.01 - Thermo Fisher Exhibit Showcase Session - The Way We Test Matters for Patient Outcomes

      12:15 - 13:15  |  Presenting Author(s): Anagh Vora

      • Abstract

      Abstract not provided