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Javier De Castro Carpeno

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    PC02 - Combining with Chemo: Old School Is New Again (ID 84)

    • Event: WCLC 2019
    • Type: Pro-Con Session
    • Track: Advanced NSCLC
    • Presentations: 4
    • Now Available
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      PC02.01 - TKIs Should Be Given as Single Agent (Now Available) (ID 3561)

      14:00 - 15:30  |  Presenting Author(s): Tony Mok

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PC02.02 - TKIs Should Be Given with Chemo (Now Available) (ID 3562)

      14:00 - 15:30  |  Presenting Author(s): Rafael Rosell

      • Abstract
      • Presentation
      • Slides

      Abstract

      TKIs Should Be Given with Chemotherapy. This is an open question, with some pros and cons, mainly due to the complexities of chemotherapy activity regarding genetic alterations. However, there are several promising hints that the combination could be useful, but not all chemotherapeutic drugs prove beneficial. This information will be provided in the presentation.

      Resistance to erlotinib and, in general, to any generation of EGFR TKIs, is heterogeneous and requires the comprehensive dynamic molecular profiling of the tumor with either tissue, liquid biopsies, or both. Before the development of the third-generation EGFR TKIs, at the time of progression to erlotinib or gefitinib, patients were successfully treated with chemotherapy [Sequist et al Sci Trans Med 2011]. The alternation of chemotherapy and EGFR TKIs merits revisiting. The intercalation of erlotinib with chemotherapy has shown a median PFS of 16.8 months in EGFR-mutant NSCLC patients [Wu et al Lanect Oncol 2013]. The most salient biological concept to re-address the contribution of chemotherapy in EGFR-mutant NSCLC is the fact that nuclear cyclic GMP-AMP (cGAMP) synthase (cGAS) expression suppresses DNA repair and, therefore, can enhance the activity of EGFR TKIs. Preclinical data strongly favors this model, showing that etoposide or other chemotherapeutic drugs can promote the translocation of cGAS to the nucleus by phosphorylation of cGAS on the tyrosine residue 215. In the nucleus, cGAS is recruited to double stranded breaks, interacting with PARP1. The cGAS-PARP1 interaction jeopardizes the generation of the PARP1-Timeless complex and suppresses homologous recombination [Liu et al Nature 2018]. The fact that cGAS transcripts are increased in NSCLC is of clinical interest, indicating that cGAS could be a new biomarker involved in the response to immune checkpoint inhibitors [Gui et al Nature 2019].

      Multilayer research sheds light on potential safe and active combinatory therapies in EGFR-mutant NSCLC and many therapeutic approaches converge in the complex signaling pathway crosstalk. Perhaps tumor heterogeneity is not the major difficulty and the mechanisms of resistance are more dependent on the capacity of tumor cells to re-wire and re-program the signaling pathways that they use to grow and migrate [Karachaliou et al EBioMedicine 2018]. Epi-transcriptomics are also involved in resistance to EGFR TKIs (Figure) [Zanconato et al Nat Med 2018]. Several chromatin regulators have emerged as druggable targets, including bromodomain-containing protein 4 (BRD4). BRD4 interacts with YAP1, and Bromodomain and Extra-Terminal motif (BET) inhibitors impair the expression of YAP1 direct target genes, including AXL, FST1 and aurora A [Zanconato et al Nat Med 2018]. We have recently reported that the combination of EGFR TKIs with barasertib, an aurora kinase B inhibitor, illustrates a strong antiproliferative activity in a broad panel of EGFR-mutant resistant cell lines [Bertran-Alamillo Nat Comm 2019].

      DNA repair modulators may be associated with resistance to EGFR TKIs. In our original study of erlotinib in EGFR-mutant NSCLC [Rosell et al NEJM 2009], we explored the role of DNA repair genes on the treatment outcome. Among several transcripts examined, breast cancer type 1 susceptibility (BRCA1) gene mRNA surfaced as relevant in the repair of erlotinib-induced DNA damage through an H2A histone family member X (H2AX)-independent pathway [Rosell et al Clin Cancer Res 2011]. Normally, DNA damage repair involves a homologous recommendation, through H2AX [Wang et al Science 2007]. Patients with low BRCA1 mRNA expression had significantly longer PFS than patients with high BRCA1 mRNA levels, and BRCA1 levels were an independent predictor of PFS in the Cox-multivariate regression analysis.

      Finally, turning off the DNA damage checkpoint after DNA repair involves the removal of phosphorylated H2AX from the chromatin, followed by its replacement with canonical H2A. This exchange of phosphorylated H2AX for H2A is mediated by facilitates of chromatin transcription (FACT) (Figure). The ability of FACT to remove phosphorylated H2AX from the chromatin is inhibited by PARP1 [Rosell et al Clin Cancer Res 2011]. A novel class of drugs, curaxins, act as a chromatin trapping of the FACT, suppressing simultaneously NF-ĸB signaling and promoting activation of p53 [Gasparian et al Sci Trans Med 2011]. The combination of erlotinib with curaxins, or FACT inhibitors, like CBL0137 [Lindner et al Cancer Res 2018], may be a significant advance in the field of EGFR-mutant NSCLC therapy.figure.jpg

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      PC02.03 - IO Should Be Given as a Single Agent (Now Available) (ID 3563)

      14:00 - 15:30  |  Presenting Author(s): Julie R Brahmer

      • Abstract
      • Presentation
      • Slides

      Abstract

      Programmed cell death 1 (PD-1) checkpoint pathway inhibitors have greatly changed the treatment paradigm for advanced stage non-small cell lung cancer (NSCLC). Durvalumab is approved for use as a single agent after chemotherapy combined with radiation for stage 3 NSCLC.(1) Pembrolizumab is approved for use in the first line treatment setting for advanced NSCLC not amenable to radiation for patients whose tumor has a tumor proportion score (TPS) of 1% or greater in the United States.(2) For patients whose tumor has a TPS of > 50%, it is approved for use in the first-line treatment setting in multiple countries throughout the world.(3) However, PD-1 checkpoint blockade combinations, either anti-PD1 or anti-PD-L1 antibodies, with chemotherapy regardless of PD-L1 status have shown benefit as well. (4,5,6)

      Single agent immunotherapy (IO) has several advantages. Cost of combination therapy is an issue. While these PD-1 pathway blocking antibodies are expensive as single agents, combining them with chemotherapy adds to the cost, time in infusion, and adds chemotherapy related side effects. So, if patients can, single agent immunotherapy is still preferred, particularly in a population i.e. TPS > 50% who is more likely to benefit compared to chemotherapy. Some would say the same is true for patients with TPS > 1, but here the data for single agent IO compared to combinations with chemotherapy is mixed. While trials comparing this scenario, i.e. comparing single agent PD-1 antibody compared to chemotherapy plus IO, head to head have not yet been done, it is hard not to do cross trial comparisons as seen in table 1. Clearly though, chemotherapy and IO combinations have increased objective response rates regardless of PD-L1 TPS status where response rates range from 57.9%-62.1%.(4,5,6,7,10)

      While combinations with chemotherapy show increased response rate regardless of PD-L1 TPS, chemotherapy can have deleterious effects on the immune system. (8) Chemotherapy can alter immune function by causing lymphopenia. Steroids, added to chemotherapy regimens to prevent allergic reactions and control nausea, can suppress pro-inflammatory cytokines and impair Natural Killer (NK) cell function and dendritic cell differentiation or activation. Taxanes specifically can cause inhibition of T-cell and NK-cell activation. Thus, these combinations may prevent immune activation and suppress immune memory. Duration of response in single agent IO in the first line treatment setting is 16.8-20.2+ month.(9,2,3) The duration of response in the IO plus chemotherapy patient population is 7.7-11.2 months.(4,5,6) The data from the chemotherapy IO combinations is too immature to know what the potential five-year survival is compared to the impressive 23.2% 5 year survival rate of the initial trial of pembrolizumab in the treatment-naïve setting(Keynote 001).(9)

      Immunotherapy, particularly PD-1 pathway checkpoint antibodies, have drastically changed the treatment landscape for advanced stage lung cancer patients. Single agent pembrolizumab particularly in patients with TPS > 50% lung cancer results in an impressive long term survival that is not seen with chemotherapy alone. Combining immunotherapy agents with chemotherapy increases disease response but long term survival outcome data and duration of response is immature.

      Table 1 – Overview of Results in NSCLC PD-L1 TPS > 50% patient population

      KeyNote 0243

      KeyNote 0422

      KeyNote 1894,10

      KeyNote 4076

      ORR

      44.8%

      39.5%

      62.1%

      60.3%

      DOR (mo)

      NR (1.9-14.5+)

      20.2

      15.1

      Not reported

      mPFS (mo)

      10.3

      HR 0.5 (0.37-0.68), p<0.001

      7.1

      HR 0.81 (0.67-0.99), p=0.017

      11.1

      HR 0.36 (0.26-0.51)

      8

      HR 0.37 (0.24-0.58)

      mOS (mo)

      30

      HR 0.63 (0.47-0.86), p=0.002

      20

      HR 0.69 (0.56-0.85), p=0.0003

      NR

      HR 0.59 (0.39-0.88)

      NR

      HR 0.64 (0.37-1.10)

      2 year OS

      51.5%

      44.7%

      51.9%

      Not reported

      NR=not reached, ORR=overall response rate, DOR=duration of response, mPFS=median progression free survival, mo=months, mOS=median overall survival, OS=overall survival

      1-Antonia SJ, Villegas A, Daniel D et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350.

      2-Mok TSK, Wu YL, Kubaba I et al. Pembrolizumab versus Chemotherapy for Previously Untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomized, open-label, controlled, phase 3 trial. Lancet 2019 May 4:383(10183):1819-1830.

      3-Reck M, Rodriquez-Abreu D, Robinson AG et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833.

      4-Gandhi L, Rodriquez-Abreu D, Gadgeel S et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092.

      5-Socinski MA, Jotte RM, Cappuzzo F et al. Atezolizumab for First-Line treatment of Metastatic Nonsqumaous NSCLC. N Engl J Med 2018 Jun 14;378(24):2288-2301.

      6-Paz-Ares L, Alexander L, Vicente D et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med 2018;379:2040-2051.

      7-Reck M, Rodriquez-Abreu D, Robinson AG et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer with PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol 2019 Mar 1;37(7):537-546.

      8-Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological Aspects of Cancer Chemotherapy, Nature Reviews Immunology 2008 (8), 59-73.

      9-Garon, E, Hellmqann M, Carcereny Costa E et al. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. J Clin Oncol 37, 2019(suppl; abstr LBA9015).

      10-Gadgeel S, Garassino M, Esteban E et al. KEYNOTE-189: Updated Overall Survival and Progression After the Next Line of therapy with Pembrolizumab plus Chemotherapy with Pemetrexe3d and Platinum vs Placebo Plus Chemotherapy for Metastatic Nonsquamous NSCLC. J Clin Oncol 37, 2019 (Suppl; abstr LBA9013).

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      PC02.04 - IO Should Be Given with Chemo (Now Available) (ID 3564)

      14:00 - 15:30  |  Presenting Author(s): Luis Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lung cancer is the leading cause of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for almost 85% of all cases. The prognosis of NSCLC patients remains quite unsatisfactory due to the frequent advanced disease stage at diagnosis and the relatively low efficacy of the available systemic treatments. Of note, over the las few years significant progress as inhibitors of programmed death-1 (PD-1) and its ligand PD-L1 have proven to be effective therapies in metastatic NSCLC lacking sensitizing EGFR or ALK mutations, initially in pretreated patients. Subsequently, in metastatic NSCLC patients with PD-L1 expression of at least 50% on tumor cells, upfront pembrolizumab improved median progression-free survival (PFS) and overall survival (OS) compared to standard platinum-based chemotherapy. However, patients with a tumor proportion score (TPS) of 50% or greater represent only some 30% of those with NSCLC, and progression during the first three months is frequent in one third of the cases. To enhance the immune response through PD-1 inhibition, several studies have combined the potential immunogenic effects of cytotoxic chemotherapy with immune checkpoint inhibitors (ICPI), particularly of some chemotherapy regimens such as those pemetrexed-based. The first study that gave some important information regarding the efficacy of combining IO and chemotherapy was Keynote 021, randomized phase II trial of carboplatin plus pemetrexed with and without pembrolizumab. It showed significantly better response rates (RR) and longer PFS with the addition of pembrolizumab to chemotherapy. Over the last two years at least 6 other phase III clinical trials with pembrolizumab (KN 189 and KN 407) have showed the benefits of combined chemotherapy plus IO therapy in terms of PFS and OS (HR 0.49-0.64). Consistent data have been achieved on atezolizumab trials, although the magnitude of the OS benefit (HR 0.78-0.93) have been somehow lower. Randomized studies with nivolumab, durvalumab and avelumab are expected to be reported in the near future. Chemo-immunotherapy combinations are associated with the expected toxicities of chemotherapy and IO on their own.

      At present, for patients with tumors with TPS >50%, there are no comparative trials of IO monotherapy (e.g. pembrolizumab) as compared to chemotherapy. Across trial comparisons may support the use of IO monotherapy for most of cases. Chemo-IO regimens may be considered for patients requiring rapid responses (e.g. symptomatic patients) or those with aggressive disease. In patients, whose tumors express PD-L1 in 1-49% of cells, chemo-IO combinations are seen as the best treatment options. Of note, in the IMPOWER 150 trial, patients with EGFR/ALK aberrations also benefitted from the addition of atezolizumab to the paclitaxel/carboplatin/bevacizumab regimen. In patients with tumors with negative expression of PD-L1 the benefits on PFS were more debatable but the pembrolizumab-based combos, and to some extend those with atezolizumab, resulted in prolonged survival. The value of certain genomic aberrations (e.g. Keap or LKB1) or low tumor mutational burden (TMB) as a predictive tool in this setting needs further validation. In addition, the results of several ongoing combination studies (CheckMate-9LA, POSEIDON ) investigating two and four drug regimens of PD-(L)1 plus CTLA-4 inhibition with/without chemotherapy are eagerly awaited and will reveal further knowledge of efficacy and tolerability in this setting.

      References

      Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. . Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. (2015) 373:1627–39.

      Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. (2016) 375:1823–33.

      Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. (2016) 17:1497–508.

      Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. (2018) 378:2078–92.

      Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379: 2040-2051.

      Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018; 378: 2093-2104.

      Jotte RM, Cappuzzo F, Vynnychenko I, Stroyakovskiy D, Abreu DR, Hussein MA, et al. IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. (2018) 36:LBA9000–LBA9000. 10.1200/JCO.2018.36.18_suppl.LBA9000.

      Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al.. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. (2018) 378:2288–301.

      Socinski MA, Jotte RM, Cappuzzo F, Orlandi FJ, Stroyakovskiy D, Nogami N, et al. Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. J Clin Oncol. (2018) 36:9002.

      Papadimitrakopoulou V, Cobo M, Bordoni R, Dubray-Longeras P, Szalai Z, Ursol G, et al. IMpower132: PFS and safety results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in stage IV non-squamous NSCLC. In: International Association for the Study of Lung Cancer's (IASLC) 2018 World Conference on Lung Cancer (WCLC); 2018 Sept 23-26. Toronto, ON: (2018).

      West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019; 20: 924-937.

      Borghaei H, Hellmann MD, Paz-Ares LG, Ramalingam SS, Reck M, O'Byrne KJ, et al. Nivolumab (Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with < 1% tumor PD-L1 expression: results from CheckMate 227. J Clin Oncol. (2018) 36:9001 10.1200/JCO.2018.36.15_suppl.900.

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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-30 - RECIST and iRECIST Comparison in a Cohort of Patients with Advanced NSCLC Treated with Immunotherapy: Preliminary Study (Now Available) (ID 2563)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Nivolumab, Pembrolizumab and Atezolizumab are anti-programmed death-receptor-1 (PD-1) and anti-programmed-death-ligand 1 (PD-L1) immunotherapy agents used in the treatment of advanced non-small cell lung cancer (NSCLC). Howewer, its radiological evaluation is challenging because of atypical patterns of response and immune-related adverse events. This study aims to (i) compare the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, with the Immune RECIST (iRECIST) and (ii) explore the association of response patterns and clinical outcome.

      Method

      We conducted a retrospective study of previously treated patients with advanced NSCLC who received Nivolumab, Pembrolizumab or Atezolizumab (first and second line). All CT scans were reviewed by two radiologists specialized in immunotherapy evaluation (1 senior, 1 junior). Tumor response was assessed according to both RECIST v1.1 and iRECIST C.

      Result

      Were included 39 patients (27 male, 12 female) between November 2014 and December 2018 with advanced NSCLC. Median of age was 64 years (range 43 to 86). 13 patients (33,3 %) were treated with Nivolumab, 18 patients (46,1 %) with Pembrolizumab and 8 patients (20,5 %) with Atezolizumab. Among of 100% of patients included, 35,9 % showed partial response (PR), 20,5% stable disease (SD) with RECIST and iRECIST criteria. 43,6 % of patients showed progressive disease (PD) with RECIST criteria but only 4 of them were confirmed progressive disease (iCPD) with iRECIST criteria (2 truly progressed and died, 1 showed PR with the treatment and 1 reached SD). 8 patients with PD (20,5 %) could not be confirmed with iRECIST, remaining as unconfirmed progressive disease (iUPD), 5 of them because of patient’s death, 1 because a change of therapy was performed and 2 because they reached SD within the treatment. The remaining 4 patients with PD presented improvement within the treatment after the initial progression (pseudoprogression).

      Conclusion

      In our study, both RECIST 1.1 and iRECIST criteria were valid for measuring the effectiveness of the treatment with Nivolumab, Pembrolizumab and Atezolizumab. No differences were found in the assessment of PR and SD.

      13 differences were detected between RECIST and iRECIST in the assessment of PD. RECIST criteria underestimated more the benefit of the treatment compared with iRECIST, but was better detecting true PD resulting in patient’s death than iRECIST (which could not always confirm the progression).

      Given the relatively small number of patients studied, further study is warranted on whether RECIST and iRECIST criteria are equivalent to evaluate new immunotherapy treatment in NSLC.

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    EP1.06 - Mesothelioma (ID 196)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.06-02 - Association of Inflammatory Biomarkers with Overall Survival in Patients with Advanced Malignant Pleural Mesothelioma (Now Available) (ID 1964)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      The inflammation process has been proposed as a mechanism of immunoresistance in patients with cancer, promoting cancer growth and dissemination. Derived neutrophil to lymphocyte ratio (dNLR) greater than 3 and lactate dehydrogenase (LDH) level greater than upper limit of normal (ULN) are associated with poor outcomes in patients with advanced non–small cell lung cancer. The aim of this study is to determine whether pretreatment levels of dNLR and LDH as well as PD-L1 status are associated with overall survival in patients with malignant pleural mesothelioma.

      Method

      We conducted a retrospective study, which included all patients with malignant pleural mesothelioma diagnosed in a tertiary referral hospital from December 2009 to March 2019. PDL1 status, complete blood cell counts and LDH levels were collected. A descriptive analysis was carried out, followed by a survival analysis using the Kaplan-Meier estimator.

      Result

      We selected 25 patients. No correlation was found between dNLR and LDH levels. 5 patients (20%) had a dNLR greater than 3, of which 3 patients had stable disease and 2 patients received supportive care. Patients with a dNLR greater than 3 had a median overall survival (mOS) of 8,5 months, whereas patients with a dNLR less than 3 had a mOS of 17,0 months, with statistically significant differences (P:0.038). 2 patients (8%) had a LDH level greater than ULN, of which 1 patient achieved a partial response and 1 patient had stable disease. Regarding the LDH level no difference in overall survival was found.

      Regarding to the PD-L1 status, 10 (40%) of 25 patients had PD-L1 ≥ 1%, 8 (32%) had PD-L1 < 1% and 7 (28%) had unknown PD-L1. Patients with PD-L1 ≥ 1% had a mOS of 8,5 months, whereas patients with PD-L1 <1% had a mOS of 15,7 months, with no statistically significant association (P> 0.05).

      Conclusion

      In our sample, pretreatment levels of dNLR greater than 3 were correlated with worse overall survival in patients with malignant pleural mesothelioma. Furthermore, pretreatment levels of LDH greater than ULN and PD-L1 greater than or equal to 1% could be correlated with worse overall survival, although due to the size of our sample we are not able to conclude statistical significance. Further studies are needed to explore this relationship.

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      EP1.06-09 - Mesothelial Tumors Registry in Spain: A Retrospective Multicenter Study (Now Available) (ID 2327)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Malignant mesothelioma is an unusual tumor associated with poor prognosis. Currently, there are no effective treatments after the progression to the first line. The aim of this study is to analyze the experience in 7 spanish centers.

      Method

      We conducted a retrospective analysis including patients with malignant mesotheliomas of 7 centers in Spain. Demographic, clinical and pathological variables, tumor response, progression date and death were collected.

      Result

      We enrolled 63 patients with diagnosis of malignant mesothelioma. The average age was 70 years. 73,4% were men and 26,4% women. The most frequent location was the pleural (78,1%) and biopsy was the main diagnostic method (92,2%). 76,6% were diagnosed as epitheloid mesothelioma subtype, whereas sarcomatoid and mixed subtypes were less frequent. Tumor in stage IV was presented at diagnosis in 75 % cases. The most frequent first treatment was chemotherapy, 95,2% of patients received treatment based on platinum doublet with pemetrexed, followed by pemetrexed maintenance. Best response was partial response in 20,6% , stable disease in 41,3% , complete response in 22,2% and progressive disease in 15,9%.The median progression free survival of the sample was 8,8 months, and the median overall survival was 12 months.

      Conclusion

      The demographics and baseline characteristics as well as the survival data obtained in our sample are consistent with the previously reported.

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      EP1.06-11 - Advanced Malignant Pleural Mesothelioma: A Single Institution Experience (Now Available) (ID 1993)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Malignant pleural mesothelioma is a rare and highly aggressive tumor that typically presents with advanced disease. The prognosis of patients with malignant pleural mesothelioma is poor and there is currently a lack of effective treatment options. The aim of this study is to analyze the experience of our center in the management of this pathology.

      Method

      We conducted a retrospective study, which included all patients with malignant pleural mesothelioma diagnosed in a tertiary referral hospital from December 2009 to March 2019. Data regarding baseline characteristics, treatment response and survival were collected. A descriptive analysis was carried out, followed by a survival analysis using the Kaplan-Meier estimator.

      Result

      We selected 25 patients. Table 1 summarizes the main sociodemographic characteristics, the histological subtype and the stage.

      Table 1 Nº (%)

      Sex: Male/Female

      19 (76%) / 6 (24%)

      Age (years):

      71 (51 – 89)

      Histology:

      – Epithelioid mesothelioma

      – Sarcomatoid mesothelioma

      – Mixed mesothelioma

      22 (88%)

      1 (4%)

      2 (6%)

      Stage:

      – Stage III

      – Stage IV

      4 (16%)

      21 (84%)

      22 (88%) of 25 patients received first line chemotherapy with platinum doublet with pemetrexed followed by pemetrexed maintenance and 3 (12%) received palliative care. The proportion of patients who received six cycles of platinum doublet with pemetrexed was 55%. 5 (20%) of 22 patients who received first line chemotherapy with platinum doublet with pemetrexed achieved a partial response, 15 (60%) had stable disease and 2 (8%) experienced disease progression.

      After a median follow-up duration of 15,17 months, 19 (76%) patients had died. The median progression free survival was 13,1 months (IC 95%: 6,7 – 19,5), and the median overall survival was 15,7 months (IC 95%: 11,3 – 20,0). The major cause of death was cancer in 18 patients (95%) and 1 patient dead of heart disease.

      Conclusion

      Demographics and baseline characteristics as well as the survival data obtained in our sample are consistent with the previously reported. Further studies are needed to determine other treatment options to improve the prognosis of these patients.

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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-20 - Retrospective Study About the Impact of Metastatic Site in Small Cell Lung Cancer (Now Available) (ID 1980)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Small cell lung cancer (SCLC) is a very aggressive type of lung cancer. It is characterized by a high cellular proliferation and an early development of widespread metastases (nearly 70% of patients presents macroscopic metastases at diagnosis). SCLC spread mainly to bone, brain and liver. In extensive disease, metastatic involvement of the liver, bone and central nervous system seems to have a worse prognosis comparing with other sites, though the studies are quite inconclusive.

      Method

      We conducted a descriptive and retrospective study including all patients diagnosed with metastatic SCLC between January 2012 and December 2018. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the impact of the metastatic involvement (depending on the localization) at diagnosis and at recurrence.

      Result

      Of the 58 patients included, 58.6% presents liver involvement at diagnosis. These patients present a worse overall survival (OS), with a mean of 1.9 months, and a clear trend to worse progression-free survival (PFS, with a mean of 5.6 months (P=0.56). Bone involvement was presented in 41.4% of the patients. No difference was observed neither in OS (with a median of 6 vs 7.9 months) nor PFS (3.9 vs 3.3 months). Lastly, only the 19% present brain metastases at diagnosis, and it didn’t show significant differences in OS (8.3 vs 6.7 months) but it did in SLP (2.6 vs 5 months). When the tumor relapses, it usually does in multiple localizations (51.3%) and the main organ involved is the lung (78.3%). It didn´t show any difference in prognostic between sites.

      Conclusion

      SCLC is a very aggressive tumor. Due to its biological behavior, a large proportion of the patients presents an advanced staged at diagnosis. In extensive disease, the number of organ sites involved is related to prognosis, but it´s not clear which localizations have a greater impact on survival rates. In our studies, liver and bone metastases are related to worse prognosis and short survival. Surprising, in our series, brain metastases don´t seem to impact in patient’s prognosis. When the tumor relapses, tumor extent (limited vs extensive) is a factor that affects the prognosis. However, in our experience, there are not clear differences between one or another, all of them related to poor prognosis. More studies will be needed to be able to clarify the prognostic impact of the metastases site, both at diagnosis and relapse.

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      EP1.12-26 - Retrospective Study About the Impact of Brain Metastases and Cranial Irradiation in Small Cell Lung Cancer (Now Available) (ID 1987)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Small cell lung cancer (SCLC) is a very aggressive type of lung cancer. Due to this behavior, it presents early development of metastases. Brain metastases (BM) are very common and are related with a great impact on both survival and quality of life. Prophylactic cranial irradiation (PCI) is used for patients without detectable brain metastases, improving survival and decreasing the incidence of brain relapses (BR). Cranial irradiation (CI) for affected patients are usually used in patients with clinical BM, but its benefits are less clear.

      Method

      We conducted a descriptive and retrospective study including all patients diagnosed with SCLC tumor between January 2012 and December 2018 (both localized and metastatic). We study the impact of PCI and CI in both patients with/without BM at diagnosis. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival and the impact of the radiotherapy treatment.

      Result

      Of the 98 patients included, 60.2% presents extensive-stage, while 39% were locally advanced. Of the advanced stages, only 18.4% presented brain involvement at the diagnosis. 34.7% of the patients received RT at the diagnosis (37.5% PCI and 50% of the patients with BM received CI).

      Over the course of the disease, 35.1% of the patients present BR. 67.6% of the patients treated with RT at diagnosis (both PCI and CI) relapsed in the brain, meanwhile, the 54.8% in the group without RT (no significant differences). However, in the RT group, 69.5% of patients relapse outside the brain (mainly the lung). Chemosensitive didn´t show any relation with the incidence of BR (30.4% RT group vs. 35.7% in no-RT group). Overall, there were no significant differences in survival (p 0.19) between the group treated with RT (both PCI and CI) and the group which didn´t.

      Conclusion

      SCLC presents early dissemination. Brain is one of the main organs involved. PCI for patients without detectable BM decrease the incidence of brain relapses and improve survival. The impact of CI is less clear in patients that already have BM. Surprisingly, in our series, we didn´t find any difference with PCI or CI in overall survival and BR. A high proportion of the patients in both groups (with/without BM at diagnosis) didn´t receive radiotherapy, due to a very poor clinical status (which can may lead to bias). More studies will be needed to be able to clarify the prognostic impact of these metastases and the effectiveness of this treatment nowadays.

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      EP1.12-29 - Retrospective Study About Small Cell Lung Cancer: Our Experience in a Spanish Hospital (Now Available) (ID 1976)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Incidence of small cell lung cancer (SCLC) has been decreased during the last decades. This neoplasm appears almost exclusively in smokers and it is characterized by aggressive biology and early development of metastases. Due to this aggressiveness, a large proportion of patients present a poor performance status at the time of diagnosis. Though the tumor is initially highly responsive to therapies, most of the patients will relapse after treatment. The prognosis is generally poor, even in limited stage disease.

      Method

      We conducted a descriptive and retrospective study including all patients diagnosed with SCLC tumor between January 2012 and December 2018 (both localized and metastatic forms were included). A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival.

      Result

      diagnosed in advanced stages (60.2%), while 29.6% were locally advanced and only 8.2%, localized. In metastatic stage, the main organ affected was the liver (35.7%), followed by the bone (24.5%). Only 12% presented brain metastases at the diagnosis. The vast majority were smokers (68.4%) or ex-smokers (27.6%), with only one patient that had never smoked.

      The 78.4% of the patients received chemotherapy (36.7% with concomitant radiotherapy). After the initial treatment, up to 55.4% of the patients recurred, mainly involving various localizations (50%). Only 39% received a second line of chemotherapy, and 24% a third line.

      At the end of the study, 84.6% of the patients had died (median of 19.7 months since diagnosis). Log-rank analysis (Kaplan-Meier estimates) showed significant differences (p<0.05) between tumor stages and platinum-sensitive status. On the contrary, there wasn´t significant difference related to sex, smoke status, type of recurrence or type of chemotherapy chosen in second line.

      Conclusion

      SCLC is heavily related with smoke. Most of them exhibit an aggressive behavior, with an advanced stage at diagnosis (in our study, up to 60.2%, and 29.6% locally advanced). Thought usually presents high chemosensitivity, most of the patients recur. At this point, the prognosis is poor, with a low benefit with the treatment, in our series regardless of the drug. Unlike the previous series, we haven´t seen a worse outcome related to sex or smoke status. More studies will be needed to be able to clarify the prognostic impact of factors such as the smoke status, sex, type of relapse or second line treatment.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-31 - Retrospective Study About EGFR Mutations in Lung Cancer: Our Experience in a Spanish Hospital (Now Available) (ID 1995)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are observed in approximately 15% of lung adenocarcinomas and usually occur in nonsmokers. The detection of these mutations can be detected either in liquid biopsies or solid tissue biopsies. EGFR mutations are a predictive biomarker for high response and longer survival (both progression-free and overall) with tyrosine kinase inhibitors (TKIs), namely gefitinib, erlotinib, afatinib and osimertinib.

      Method

      We conducted a descriptive and retrospective study including all patients diagnosed with EGFR mutations between January 2007 and September 2018 (both locally advanced and metastatic forms were included).

      Result

      Of the 67 patients, the mean age was 67.2 years. The majority were adenocarcinoma (82.5%), with only 7.9% of squamous and 6.4% large cell carcinoma. The main mutations registered were exon 21 deletion (41%) and exon 19 deletion (4.9%). Only 24.6% had history of smoking. 71.6% of patients present stage IV disease at diagnosis. The main organ involved was the bone (45.8%), followed by the lung (44.1%) and brain (25.4%). Also 13.6% presents pleural, 10.2% liver, 5.1% adrenal and 5.6% lymph node involvement.

      84.1% of the patients were treated with TKIs (erlotinib 49.2%, gefitinib 16% and afatinib 19%) while 16% were treated with chemotherapy. With first line treatment, 94.7%presented disease control (41.8% partial response, 41.9% stable disease and 11% complete response). With a mean of 23.6 months, 56.9% of them progressed, mainly involving the lung (28.6%) and the bone (20.6%). Only 9.5% presented brain progression. At the end of the study, 34% had died (overall survival´s mean of 27.5 months).

      Conclusion

      In patients with oncogenic driver mutations in EGFR, treatment with TKIs results in a better outcome than standard chemotherapy. This mutation predicts sensitivity to EGFR (our study shows up to 94.7% presents some type of response). Also, this response is longer (23.6 months in our experience) and better tolerated than chemotherapy. Overall survival of these patients is longer too, in our series, round to 27.5 months of overall survival, and mainly related to the tumor stages. More studies will be needed to be able to clarify the prognostic impact of factors such as the smoke status, sex, type of relapse or second line treatment.

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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-01 - A Spanish Initiative to Know the Unmet Needs of Women with Lung Cancer: "Circulos Program" (Now Available) (ID 1847)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      The personal and family impact of an oncological disease can only be adequately understood and managed from a biopsychosocial perspective. Lung cancer experience has a profound impact on the well-being of both patient and family caregiver and is largely influenced by communication within the family environment. Lung cancer impact can be especially significant when women are affected.

      Method

      The objective of this study was to develop an informative program for women with lung cancer, implementing the development of strategies in order to get a deepening knowledge of their perceived needs. Additionally, we aimed to define and design new useful resources that may help other women with lung cancer. A qualitative research allowed to collect data on the experiences in the circle of women and their families, and the identification of the needs and the coping resources used of the participants. The collection of these data was what led to the development of the tools used to develop the support strategies.

      Result

      A total of 10 women with lung cancer from Galicia (Spain) participated in 7 sessions. At the personal and psychological level in the women circle, needs were related to improve medical information they get from their physicians, share information and experiences with women in the same situation, more holistic-human care, and the need for more supporting groups. About the social and labor environment, they expressed concern about the social stigma associated with lung cancer, and the culpability for having smoked as well as the concern related to the interruption of working life. The family environment also expressed the need for emotional support and preparation for families and caregivers to be able to support the patient, the need to provide them with strategies to improve the situation, and the need to overcome initial isolation through working groups. Regarding resources, women´s circle was mainly focused on occupying time with new activities, humor and not stigmatizing the disease and the professionals who assist them.

      Conclusion

      “Círculos program”, even being a pilot program, show the benefits of a more humane approach to the treatment of lung cancer in women, with a better understanding of patients and families needs. More similar programs should be done in order to improve the quality of life of these patients and their transit through this disease.

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    EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.18-28 - Neoadjuvant Therapy Among Patients Undergoing Resection for Non-Small-Cell Lung Cancer: A Single Institution Experience (Now Available) (ID 2002)

      08:00 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer deaths worldwide. Surgery alone results in poor overall survival in patients with stage III non-small cell lung cancer (NSCLC). Neoadjuvant therapy offers the ability to treat micrometastatic tumor cell dissemination preoperatively and increased resectability due to tumor regression. The aim of this study is to analyze the experience of our center and to identify clinical and pathological characteristics related to greater relapse-free survival (RFS).

      Method

      We conducted a retrospective study, which included all patients with NSCLC treated with neoadjuvant therapy follow by surgery in a tertiary referral hospital from April 2013 to March 2019. Data regarding clinical and pathological characteristics, treatment response, type of surgery and survival were collected.

      Result

      We selected 10 patients. Table 1 summarizes the main sociodemographic characteristics, the histological subtype, the stage, the regimens of neoadjuvant therapy and the types of surgery.

      Table 1 Nº (%)
      Sex: Male/Female 6 (60%) / 4 (40%)
      Age (years): 62 (44 – 77)

      Performance status:

      – 0

      – 1

      6 (60%)

      4 (40%)

      Smoking:

      – No

      – Yes

      1 (10%)

      9 (90%)

      Weight loss before diagnosis:

      – High (≥5%)

      – Low (<5%)

      1 (10%)

      9 (90%)

      Histology:

      – Squamous cell carcinoma

      – Adenocarcinoma

      – Large-cell cancer

      3 (30%)

      6 (60%)

      1 (10%)

      Stage:

      – Stage IIIA

      – Stage IIIB

      6 (60%)

      4 (40%)

      Node status:

      – N0

      – N1

      – N2

      3 (30%)

      1 (10%)

      6 (60%)

      ALK translocation:

      – No

      – Yes

      – Unknown

      8 (80%)

      0 (0%)

      2 (20%)

      EGFR mutation:

      – No

      – Yes

      – Unknow

      8 (80%)

      0 (0%)

      2 (20%)

      Percentage of PD-L1 at diagnosis:

      – < 1%

      – 1 – 49%

      – ≥ 50%

      – Unknow

      5 (50%)

      1 (10%)

      2 (20%)

      2 (20%)

      Neoadjuvant therapy regimens:

      – Platinum – pemetrexed

      – Platinum – vinorelbine

      – Platinum – paclitaxel – bevicizumab

      – Platinum – vinorelbine – gemcitabine

      – Platinum – paclitaxel – nivolumab

      5 (50%)

      1 (10%)

      1 (10%)

      1 (10%)

      2 (20%)

      Types of surgery:

      – Lobectomy

      – Bilobectomy

      – Pneumonectomy

      6 (60%)

      1 (10%)

      3 (30%)

      Percentage of PD-L1 after neoadjuvant therapy:

      – < 1%

      – 1 – 49%

      – ≥ 50%

      – Pathological complete remission

      – Unknow

      2 (20%)

      1 (10%)

      4 (40%)

      2 (20%)

      1 (10%)

      Regarding tumour response rates after neoadjuvant chemotherapy, 2 (20%) of 10 patients achieved a complete response and 8 (80%) achieved a partial response. Furthermore, 5 (71%) of 7 patients with mediastinal lymph node involvement achieved a nodal downstaging. Using the Wilcoxon signed-rank test, there are statistically significant differences in the stage of the patients before and after the neoadjuvant chemotherapy (Z: -2,82, p:0,005).

      After a median follow-up duration of 38 months, 5 (50%) patients had relapsed. The median RFS was 22 months (IC95%: 2–41). We did a multivariate logistic regression analysis, in which no statistically significant associations were found between clinical and pathological characteristics studied and the RFS (p>0,05).

      Conclusion

      Neoadjuvant therapy followed by surgery should be considered as standard treatment for a selective group of patients with stage III of NSCLC, in our sample all patients yielded excellent results. In the multivariate analysis no statistically significant associations were found due to the small size of our sample.

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    MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA02.01 - Reccurrence Pattern After Adjuvant Customized Chemotherapy Based on BRCA Expression Level (SCAT Trial) (Now Available) (ID 2760)

      10:30 - 12:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Presentation
      • Slides

      Background

      •Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement, (St II-IIIA). Customization is feasible in adjuvant setting (tissue availability) . Analysis of expressionin genes involved in DNA repair could be use to select CT regiment. •BRCA1 plays an important role in DNA repair pathways and functions as a differential regulator of response to cisplatin and antimicrotubuleagents. SCAT trial results found that for low BRCA1 levels subgroup Cis-Gemcitabine was superior to Cis-Docetaxel and in high BRCA1 levels subgroup Docetaxel single agent without platinum achieved similar survival to Cis-Doc. Analysis of recurrence pattern in different subgroups of the trials has been performed

      Method

      From Jun/2007 to May/2013 591 patients were screened and 500 p were included (108 in Control arm treated with Cisplatin-Docetaxel and 392 in Experimental arm treated with Cisplatin-Gemcitabine, Cisplatin-Docetaxel or Docetaxel alone according terciles BRCA1 expression level). With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence pattern are analysed in each arm and subgroup treatment and comparison are made for incidence of risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and site of metastases (liver, bone, brain)

      Result

      Cumulative recurrence 232/456 evaluable patients (p) (50.8%). Recurrence were seen in 182/354 patients treated in experimental arm and in 50/102 p treated in the control arm (RR 1.04; 0.83-1.30) (p=0.672). Majority of recurrences 159/232 (68.5%) were single site recurrence. Intrathoracic recurrences in 121/232 (52%) while extrathoracic metastatic disease 111/232 (47.8%). No significant differences were seen for single/multiple, intra/extrathoracic recurrences between experimental and control arm. More frequent distant metastatic sites were: bone (42 p), brain (38 p) and liver (11 p) In the experimental group between different treatments no significant differences were found for the overall metastatic rate or for the single/multiple, intrathoracic/extrathoracic recurrences. For specific metastatic sites related to experimental treatment a significant reduction of risk of brain metastases were found in the experimental group with high level BRCA1 treated with Docetaxel single agent (p=0.0016)

      Conclusion

      For NSCLC resected patients with lymph node involvement (Stages II-IIIA) risk of recurrence remains high with cumulative rate > 50%. There were no differences in the Relative Risk (1.04) of recurrence when control and experimental arm are compared. Majority of recurrences were single site (68.5%) and intrathoracic (52%) but distant metastases developed in 47.8% os p. More frequent metastatic site was bone, followed by brain and liver. Brain metastases risk were significant lower for patients with low BRCA1 expression treated with single agent Docetaxel

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    MA22 - Partnering with Patients to Understand Stigma, Disparities and Values Leading to Improved Lung Cancer Care (ID 154)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advocacy
    • Presentations: 1
    • Now Available
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      MA22.05 - Assessment of Gender Differences in the Psychosocial and Economic Impact on Patients with Stage IV Non-Small Cell Lung Cancer (Now Available) (ID 718)

      15:45 - 17:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Presentation
      • Slides

      Background

      Incidence of lung cancer in women is rising overtime reporting evident gender-based differences in epidemiology, biology, and treatment outcome. However, little is known about gender-differences regarding psychological, economic and social aspects. The objectives of this prospective study are to evaluate the psychosocial and economic impact of metastatic non-small cell lung cancer (NSCLC), according to gender. Additionally, to assess the emotional burden and the economic impact of the disease on the primary caregiver from a gender perspective

      Method

      Multicenter, prospective, observational, study of two cohorts of patients with metastatic NSCLC (male and female) in Oncology departments of 20 Spanish hospitals. The following measurement tools were used: the APGAR questionnaire (family functionality: adaptability, partnership, growth, affection, and resolve), the Relationship impact scale, the DUKE-UNC scale (perceived socio-affective support), the patient and the caregiver economic impact scale and the Zarit scale (caregiver burden). All questionnaires were performed at the first visit, repeated 4 months later and following the first and second disease progression.

      Result

      Of the 333 pts included, 104 were females and 229 male, of whom 63% and 97%, respectively, were smokers/ex-smokers (p=0.0001). More women than men (85% vs 70%) had adenocarcinomas . The median overall survival was longer in women but did not reach statistical significance [17.1 vs 11.0 months, HR 0.732 (95% CI 0.534 to 1.005), p=0.0524]. Most families considered themselves functional (high score in APGAR questionnaire) with no changes in their partner relationship and social support was evaluated as optimal for majority of patients. Around a quarter of interviewed patients said their economic situation was a little worse after the lung cancer diagnosis, without remarkable differences by gender. Statistically significant differences were found between both groups regarding the caregiver´s relationship to the patient (more parents were the caregiver in females than in males) (p <0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p<0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. No remarkable differences by gender were found between the different variables across the study.

      Conclusion

      This study provides a preliminary insight into gender-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a gender perspective

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.07 - Phase 3 ALUR Study of Alectinib in Pretreated ALK+ NSCLC: Final Efficacy, Safety and Targeted Genomic Sequencing Analyses (Now Available) (ID 2267)

      10:30 - 12:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Presentation
      • Slides

      Background

      The ALUR (NCT02604342) primary analysis (cut-off January 2017) demonstrated improved efficacy and safety with alectinib versus chemotherapy in patients with ALK+ NSCLC previously treated with chemotherapy and crizotinib. These patients can develop crizotinib resistance through ALK secondary mutations, but limited data exist regarding alectinib’s efficacy in patients with different post-crizotinib genetic profiles. We report final data from ALUR including treatment outcomes according to genetic profile.

      Method

      Overall, 119 patients with locally determined ALK+ NSCLC were randomised 2:1 to receive alectinib 600mg bid or chemotherapy (pemetrexed 500mg/m2 or docetaxel 75mg/m2 q3w). The primary endpoint was PFS by investigator. Targeted genomic sequencing (FoundationONE® [tissue; 315 genes] and FoundationACT® [plasma; 62 genes]) was performed retrospectively using tumour tissue (n=33) and baseline plasma (n=59).

      Result

      Final efficacy data confirmed those of the primary analysis (table). Grade ≥3 treatment-emergent adverse events were lower with alectinib (37.7%) than with chemotherapy (43.2%); adverse events causing treatment discontinuation were lower with alectinib (5.2% versus 10.8% chemotherapy), despite alectinib’s longer treatment duration. ALK fusions were confirmed retrospectively in 26/33 (78.8%) tissue and 41/59 (69.5%) plasma (post-crizotinib) samples. ORR in alectinib-treated patients with ALK fusions was 72.2% (13/18, tissue) and 63.0% (17/27, plasma) versus 0% for chemotherapy (tissue [0/8], plasma [0/14]). ALK secondary mutations were detected in 16/59 (27.1%) patients (plasma, both arms). ORR in the alectinib arm (plasma) was similar in patients with ALK fusions with (60.0%, 6/10) or without (64.7%, 11/17) ALK secondary mutations, but lower in patients with gene mutations other than ALK (23.1%, 3/13).

      Conclusion

      Final data from ALUR confirm the primary analysis, demonstrating improved efficacy and safety with alectinib versus chemotherapy in post-crizotinib ALK+ NSCLC. The role of reconfirming ALK status upon sequential ALK inhibitor treatment requires further investigation, due to the limited data and known technical challenges of plasma testing.

      Funding: F. Hoffmann-La Roche Ltd.

      table.jpg

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    OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      OA13.05 - NADIM Study: Updated Clinical Research and Outcomes (Now Available) (ID 1670)

      11:30 - 13:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Presentation
      • Slides

      Background

      Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months

      Method

      A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC in adult patients with CT plus IO as neoadjuvant treatment: 3 cycles of nivolumab (NV) 360 mg IV Q3W + paclitaxel 200 mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After completing neoadjuvant therapy, all patients underwent tumor assessment prior to surgery. Surgery was performed during the 3rd or 4th week after day 21 of the 3rd neoadjuvant treatment cycle. The study aimed to recruit 46 patients. The primary endpoint was Progression-Free Survival (PFS) at 24 months. Efficacy was explored using objective pathologic response criteria. Here we present the final data on all study patients that underwent surgical assessment.

      Result

      At the time of submission, the 46 patients had been included. None of the patients were withdrawn from the study preoperatively due to progression or toxicity. 41 patients had undergone surgery and all tumors were deemed resectable with R0 resection in all cases. Intention to treat analysis shows 35 patients (85%; 95% CI, 71; 94%) achieved major pathologic response (MPR) of which 25 (71%; 95% CI, 54; 85%) were complete pathologic responses (CPR). Downstaging was seen in 38 (93%; 95% CI, 80; 98%) of cases. The median follow-up was 13.8 months (P25; P75: 11.7; 16.6 months) for both the whole series and resected patients, and 12 month PFS was 95.7% (95% CI, 84; 99%).

      Conclusion

      This is the first multicentric study to test CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a complete pathologic response rate that is higher than ever seen previously, together with a promising PFS which may translate into increased overall survival. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.

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    OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
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      OA14.04 - Five-Year Outcomes From the Randomized, Phase 3 Trials CheckMate 017/057: Nivolumab vs Docetaxel in Previously Treated NSCLC (ID 894)

      11:30 - 13:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Historically, outcomes for advanced non-small cell lung cancer (NSCLC) have been poor, with 5-year survival rates < 5% with conventional chemotherapy. Nivolumab, a programmed death-1 (PD-1) inhibitor, was approved in 2015 for patients with previously treated advanced NSCLC based on two randomized phase 3 trials, CheckMate 017 (NCT01642004; squamous) and CheckMate 057 (NCT01673867; non-squamous), which demonstrated improved overall survival (OS) vs docetaxel. We report 5-year pooled efficacy and safety from these trials, representing the longest survival follow-up for randomized phase 3 trials of an immune checkpoint inhibitor in advanced NSCLC.

      Method

      Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG performance status (PS) ≤ 1, and progression during or after first-line platinum-based chemotherapy, were randomized 1:1 to nivolumab 3 mg/kg Q2W or docetaxel 75 mg/m2 Q3W until progression or unacceptable toxicity. After completion of the primary analyses, patients in the docetaxel arm no longer receiving benefit could cross over to receive nivolumab. OS was the primary endpoint for both studies.

      Result

      At 5-year follow-up, 50 nivolumab patients and 9 docetaxel patients were alive. Baseline characteristics of 5-year survivors in both arms were similar to the overall population and patients who survived < 1 year, except for a higher percentage of patients with ECOG PS 0 or tumor programmed death ligand-1 (PD-L1) expression ≥ 1% on nivolumab and ECOG PS 0 and Stage IIIB NSCLC on docetaxel. Nivolumab continued to show long-term OS and progression-free survival (PFS) benefit vs docetaxel with 5-year OS rates 13% vs 3% (HR, 0.68 [95% CI, 0.59–0.78]) and PFS rates 8% vs 0% (0.79 [0.68–0.92]). OS benefit with nivolumab vs docetaxel was observed across subgroups including patients with tumor PD-L1 expression < 1%, baseline liver and adrenal metastases, neutrophil-to-lymphocyte ratio < median, lactate dehydrogenase ≥ upper limit of normal or no baseline proton-pump inhibitor use. Among patients with an objective response to nivolumab (20%) or docetaxel (11%), 32% remained in response at 5 years vs none on docetaxel, with a median duration of response of 19.9 vs 5.6 months, respectively. Of the 5-year nivolumab vs docetaxel survivors, 36% vs 0% were on study drug, 20% vs 67% received subsequent immunotherapy (on or off study), and 10% vs 0% were off study drug, progression free, with no subsequent therapy. No new safety signals were observed with longer follow-up. Between 3 and 5 years’ follow-up, 8 of the 31 (26%) nivolumab-treated patients reported a treatment-related adverse event, 1 (3%) grade 3–4. The most common select adverse events (events with a potential immunological cause) were related to skin, in 4 (13%) patients, none of which were grade 3–4.

      Conclusion

      CheckMate 017 and 057 are the first phase 3 trials to report 5-year outcomes for a PD-1 inhibitor in previously treated advanced NSCLC, demonstrating a greater than 4-fold increase in 5-year OS rates with nivolumab (13%) over docetaxel (3%). Nivolumab remained well tolerated with no new safety signals.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-111 - ATEZO-BRAIN, A Single-Arm Phase II Study of Atezolizumab Combined with Chemotherapy in Stage IV NSCLC Patients with Untreated Brain Metastases (ID 733)

      09:45 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Brain metastases (BM) are a frequent complication in non-small cell lung cancer (NSCLC), have significant impact on quality of life and are associated with poor prognosis. Systemic therapies might be an alternative approach to whole brain radiotherapy (WBRT) to avoid cognitive-related adverse events. Immune checkpoint inhibitors (ICI) showed intracranial activity in advanced NSCLC patients with BM. However clinical data about efficacy and safety of immune checkpoint inhibitors in combination with chemotherapy in patients with untreated BM are limited and further research in this setting is needed. We hypothesize that addition of ICI to conventional platinum-based chemotherapy may increase intracranial tumor response and provide clinically relevant benefit in terms of PFS, OS and quality of life to the patients with asymptomatic and non-previously treated BM.

      Method

      This is an ongoing multicenter, open-label, single-arm phase 2 study (EUDRACT: 2017-005154-11) to evaluate the efficacy and safety of atezolizumab 1200 mg combined with 4-6 cycles of carboplatin AUC 5 and pemetrexed 500mg/m2 every 3 weeks followed by maintenance with atezolizumab 1200 mg plus pemetrexed 500mg/m2 every 3 weeks in stage IV non-squamous NSCLC patients with untreated synchronous BM. Patients should have multiple and measurable BM, adequate performance status and organic function, do not harbor EGFR or ALK genomic alterations, be treatment naïve and do not have any contraindication to receive immunotherapy. Exclusion criteria consist of active neurological symptoms, dexamethasone dose ≥ 4 mg QD, prior treatment with brain radiotherapy, presence of leptomeningeal carcinomatosis, spinal or hemorrhagic metastases in the central nervous system. Primary endpoints are progression-free survival (PFS) at 12 weeks according to RANO-BM and RECIST v1.1 criteria and safety based on CTCAE v4. Both primary endpoints will be assessed in 40 patients in 15 sites using a Bayesian approach. Patients will undergo tumor assessments by body CT scan and brain MRI at baseline every 6 weeks for the first 12 weeks and thereafter tumor assessments will be performed every 9 weeks until disease progression or loss of clinical benefit. Secondary endpoints: intracranial and systemic objective response rate and duration of response. Exploratory endpoints: to assess neurocognitive function and quality of life; to determine time to neurological deterioration and time to need of salvage brain radiotherapy. Enrollment started on August 2018 and currently 12 patients have been included in the study.

      Result

      Clinical trial in progress

      Conclusion

      Clinical trial in progress

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      P1.01-130 - Clinical Experience with Nintedanib in Previously Treated Non-Small Cell Lung Cancer in Spain: A Retrospective Multicenter Study (Now Available) (ID 2260)

      09:45 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer deaths worldwide. Nintedanib is a triple angiokinase inhibitor approved with docetaxel for non-small cell lung cancer after chemotherapy. The aim of this study is to analyze the efficacy and safety of nintedanib in combination with docetaxel in patients treated in various Spanish centers.

      Method

      We conducted a retrospective multicenter study, which included all patients with non-small cell lung cancer who received nintedanib with docetaxel in second o third line of treatment.

      Result

      We enrolled 124 patients from ten different Spanish centers. The male –female ratio was 3:2, with an average age of 62 years. 82,7% were smokers, 12,2% never smokers and 5,7% former smoker. The most frequent histology was adenocarcinoma (97,6%) and respect mutational state only 5 patients were EGFR mutate and 1 patient presented ALK translocation. PDL1 status was unknown in 46,3% of cases, negative in 32,5% and positive in 21,1%. The majority of patients were diagnosis in stage IV (74%) and in stage III (13,8%). In the first line, 98,4% had received platinum-based chemotherapy and 40,7 % had received previous bevacizumab therapy with an average of 4,1 cycles.

      The average of nintedanib cycles was 6 and the median time of treatment was 496 days. 65,9% of patients included had progressed to the first line in less than 9 months. The disease control rate was 61% (25,2% stable disease, 34,1% partial response and 1,6% complete response). Progression free-survival was 4,1 months and the overall survival was 26,9 months. The most common adverse events were: fatigue ( 82,1%), diarrhea (63,4%), nausea (32,5%), neutropenia (33,3%) and cough (18,2%). Thirty-one patients (25,2%) required dose adjustment (15 patients decrease to 200 mg daily and 18 patients to 300 mg daily).

      Conclusion

      The efficacy and safety of nintedanib in our cohort is similar to the previously reported. Nintedanib in combination with docetaxel is an effective treatment option for patients with advanced non-small cell lung cancer.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-12 - Preclinical Validation of an Epigenetic Panel of Seven miRNAs at Early Stages NSCLC Patients and Its Prognostic Implications (Now Available) (ID 1385)

      09:45 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Despite radical intent, many patients in early stages of NSCLC will recur. There is a need to find novel biomarkers able to help to identify patients in higher risk. Previous results from our group provide a miRNA signature from “in vitro” studies that might be involved in worst prognosis in NSCLC patients (PMID: 29158814). The main objective of this work is to analyse and compare the miRNA seven-panel signature in paired plasma (CIRmiARN) and tumor tissue samples (TmiARN) obtained from early stages NSCLC patients and to study the clinical implications.

      Method

      We conducted a descriptive study including 16 paired samples of patients diagnosed with early stage NSCLC. Both RNA from fresh tissue and plasma were extracted and the seven mRNAs levels were measured by qRTPCR(miR-7, -132, -335, -148, -10a, -124 and -9). Association between qualitative variables was analyzed using the chi-square test or Fisher's exact test. Mann-Whitney U test and the t-student test were used for qualitative and quantitative data comparison. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival and progression-free survival. Patients were also clustered in terms of tissue and plasma values, and then subgroups analyzed in terms of Survival. Difference between groups was analyzed with Cox Regression.

      Result

      There was no association between CIRmiARN and TmiARN expression levels and between clinical parameters. We found significant data associated with three miRNAs. There were significant differences (p<0.05) with low TmiR-132 expression level and worse survival and also a clear trend towards the group of patients with high levels of CIRmiR-7 and CIRmiR-124 and worst survival. Interestingly, we found an inverse correlation between CIRmiARN-132 and -124(p<0.05). Patients clustered regarding TmiR132 and CIRmiR-124 and -7levels, segregate in three clusters statistically significant in terms of survival (p<0.005), identifying a group of patients with a reduced risk of 78,6% (Hazard Ratio of 0.214 p<0,005).

      Conclusion

      Many patients diagnosed in early stages of NSCLC present a tumor relapse during the first 5 years. Genetic and epigenetic profiles help us to identify tumors with a greater risk of recurrence. In our study, we have identified three potential molecular candidates, both in liquid and tissue biopsies, which could have potential clinical use stratifying patients with higher risk of recurrence. Further studies will be needed to gain insight into the prognostic impact of these biomarkers in early and advanced stages NSCLC patients.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-16 - Early Antibiotic Use Affects the Efficacy of First Line Immunotherapy in Lung Cancer Patients but Route of Administration Seems to be Decisive (ID 1155)

      09:45 - 18:00  |  Author(s): Javier De Castro Carpeno

      • Abstract

      Background

      Several studies found that cancer patients treated with PD-1 immune checkpoint inhibitors (CKIs) who receive antibiotics (ATX) had worse efficacy outcomes because ATX can dysregulate gut microbiota. There are some data in pretreated non-small-cell lung cancer (NSCLC) and few data about the route of ATX administration, but it`s unkown whether ATX administration can also affect efficacy of CKIs in first line setting in patients treated with pembrolizumab monotherapy.

      Method

      This is a multicenter retrospective study. We included consecutive patients with advanced NSCLC with high PD-L1 expression (50%) treated with pembrolizumab monotherapy in first line, between September 2016 and March 2019, from 12 hospitals in Spain. The aim of the study was to evaluate if patients taking ATX 2 months before or within the first month after starting CKIs had worse OS, and if OS was affected by the route of administration and type of prescribed ATX.

      Result

      121 patients were evaluated. Median age was 68 years (38-88). 90 (74,4%) were male and 90 (74,4%) had PS1. Predominant histologies were adenocarcinoma (68,6%) and squamous-cell carcinoma (23,1%). Median number of cycles was 7 (1-33). Median follow-up: 6,5 months. Most were current or former smokers (95,9%). Only 1 patient had driver mutation (ALK rearrangement). 66,9% had 2 or more metastatic locations, 18,2% had central nervous system (CNS) disease, 17,4% liver metastasis, and 41,3% bone metastasis. 45,5% received ATX, 65,5% of them intravenously and 34,5% orally. Most prescribed ABX were quinolones (40,7%) and penicillin or derivatives (35,2%). 21,5% received subsequent chemotherapy. Response rate was 40,4% according to RECISTv1.1 criteria. 11% had hyperprogression and 7,2% pseudoprogression. Estimated 12-month-OS was 62% (95%CI: 49.1%-72.5%) and estimated 12-month-PFS was 44.2% (95%CI: 31.1%-56.5%) Patients who received ABX had more risk of disease progression as best response (52,2% vs 24,5%,RR: 2.1, 95%CI: 1.2-3.7, p=0.007). Patients who received ATX had shorter OS (HR:1.9, 95%CI: 1.1-3.7, p=0.047) and shorter PFS (HR:2.6, 95%CI: 1.4-4.8, p=0.002). Patients who received ATX intravenously had shorter OS than those not treated (HR:2.8, 95%CI: 1.4-5.6) and than those who received ABX orally (HR:3.5, 95%CI: 1.2-10.3, p=.025) ). Patients treated with ABX also had shorter PFS than those not treated (HR: 3.5, 95%CI:1.8-6.8, p<0.001) and than those who received ABX orally (HR: 2.2, 95%CI:1-4.8, p=0.05). Similar HR were estimated adjusting by age, gender, stage, and hepatic and bone metastasis presence. There were no OS and PFS differences between patients who received ABX orally and those who did not received them. There were no survival differences according to type of ABX.

      Conclusion

      Our results suggest that use of intravenous ABX has a negative impact on disease control rate and survival outcomes (PFS and OS) in patients with naïve advanced NSCLC and high PD-L1 expression treated with pembrolizumab monotherapy in first line setting. Patients who received oral ABX had similar efficacy than those not treated with ABX. To our knowledge, this is the first retrospective study evaluating the impact of ATX on the efficacy of CKIs in first-line treatment setting of NSCLC patients.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 5
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-10 - Real Clinical Practice Study to Evaluate 2 Line Treatment Based on Comprenhensive Genomic Profiling in NSCLC. LungONE Study (Now Available) (ID 1558)

      10:15 - 18:15  |  Presenting Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Cancer is a genomic disease and molecular-targeted therapy plays an increasingly important role in the treatment of advanced NSCLC. The current standard of care (SoC) indication for NSCLC is defined by genomic biomarkers to classify the tumor as a carrier of a therapeutic approved target. However, the current standard of practice for molecular testing in NSCLC in Spain is highly heterogeneous, depending on several factors such as hospital size, resources, laboratory equipment and experience. In addition, there are several other markers and/or genomic signatures which are not determined due to the current lack of scientific evidence, i.e. MSI, TMB, KRAS, BRAF, RET, MET, HER2 and NTKR, which could guide physician second line treatment choice, including clinical trial options. The aim of this study is to evaluate the impact on decision making in the 2nd line treatment using a comprehensive genomic profiling (CGP) in advanced/metastatic NSCLC with adenocarcinoma histology.

      Method

      Section not applicable

      Result

      Section not applicable

      Conclusion

      This is a multicenter, prospective, single-cohort study to describe the clinical management of the 2nd line SoC treatment in patients with locally advanced/metastatic NSCLC with adenocarcinoma histology, when a comprehensive genomic profile based on FoundationOne®CDx or FoundationOne® Liquid test, is provided. 12 academic institutions in Spain were selected and 180 patients were planned to be recruited. The principal objective is to evaluate if there is any change in planned 2nd line treatment decisions after receiving the CGP report. Secondary objectives for this study are:1) to identify non-previously detected actionable molecular aberrations by conventional molecular assays; 2) to evaluate the economic impact in terms of use of healthcare resources of the CGP vs. standard diagnostic panels; and 3) to describe each patient’s status 2 years after the inclusion of the last patient in the study. Patients will follow usual clinical pathways for biomarker analysis and a comprehensive genomic profiling in the remaining tissue through FoundationOne® CDx, will be conducted or liquid biopsy with FoundationOne® Liquid, if exhausted. To be enrolled in the study, patients must have an ECOG between 0 and 2 and biomarkers ALK, EGFR, ROS1 must have been assayed (negative or unknown results). Enrolment begun on October 2018 and, to date, a total of 110 patients have been included.

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      P2.01-12 - A Phase I/II Trial of IO102 and Pembrolizumab With/Without Chemotherapy as First-line Treatment of Metastatic NSCLC (ID 706)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Immunotherapy has significantly changed the treatment landscape of non-small cell lung cancer (NSCLC) with no driver mutations. However, despite the addition of anti-PD-1/PD-L1 therapies to the clinical armamentarium only a subset of patients derives durable benefit. IO102 is a novel, second generation, HLA-A unrestricted immune modulating T-win® vaccine targeting IDO. IO102 has a dual mode of action; remodulation of the tumour micro-environment through elimination of immune suppressive cells, and induction of CD8 T-cell mediated killing of IDO-expressing tumor cells. Our first-generation IDO vaccine (IO101) has shown promising antitumor activity and a favorable safety in heavily pretreated NSCLC patients (Iversen, CCR 2013).

      Method

      Phase I/II, international, multicenter, open-label, randomized trial with two parallel cohorts. Cohort A: IO102 (100µg s.c.) and pembrolizumab (200 mg) (PD-L1 ≥ 50%); Cohort B: IO102, pembrolizumab and carboplatin plus pemetrexed (PD-L1 < 50%). The maximum treatment duration is 35 cycles (app. 2 years). Key eligibility criteria include metastatic NSCLC or non-squamous NSCLC (cohort B) with no prior treatment for metastatic NSCLC and no driver mutations.

      Phase I is a non-randomized safety run-in with 6 patients per cohort investigating one dose level of the experimental arms. Only one DLT is allowed in each cohort. Phase II is following Sargent’s two-stage, three-outcome optimum design (Sargent, ClinTrial2001) with a 2:1 randomization in the cohorts. Cohort A: IO102 and pembrolizumab versus pembrolizumab alone; Cohort B: IO102, pembrolizumab and chemotherapy vs. pembrolizumab and chemotherapy. Provision of blood and tumour tissue is required for biomarker studies.

      The primary endpoint is safety and objective response rate (ORR) per RECIST 1.1 in Phases I and II, respectively. Secondary endpoints include ORR per iRECIST, duration of response, progression free survival, overall survival, and biomarkers including immunoscore in tissue, tumour mutational burden and immunomonitoring in blood.

      The study is enrolling in Europe. First patient was entered in September 2018 and recruitment is expected to continue throughout 2019: EudraCT Number 2018-000139-28 / IND Number: 018081.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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      P2.01-55 - Immunotherapy First or After Nintedanib?: A Spanish Experience (Now Available) (ID 2308)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Anti PD-1 and PD-L1 immunotherapies have demonstrated improved survival as second line treatment of patients with advanced lung cancer, and actually, this is a standard of care. In addition, Nintedanib-docetaxel is an option for few patients, and have demonstrated efficacy in second line treatment after platinum-based chemotherapy. The doubt is if immunotherapy could be change efficacy of nintedanib-docetaxel treatment.

      Method

      We conducted a retrospective multicenter study, which included all patients with non-small cell lung cancer who received nintedanib with docetaxel in second o third line of treatment. The objective of this study was to determine the efficacy of the nintedanib-docetaxel combination before and after immune checkpoint inhibitors.

      Result

      We enrolled 120 patients from 10 different Spanish centers. 72.4% had not received previous immunotherapy, while 27.6% had received it. Of those who had received previous immunotherapy: 10.6% received pembrolizumab, 10.6% received nivolumab and 3,3% received atezolizumab. Receiving previous immunotherapy had no impact on the PFS (4.5 months vs 3.2 months) or on the OS of the patients (25 months vs 20 months). Best response was partial response in 11 patients, stable disease in 11 patients and progressive disease in 10 patients. After the progression to nintedanib/docetaxel, 21.9% received immunotherapy. 15 patients received nivolumab, 10 patients atezolizumab and 2 patients pembrolizumab. Best response was partial response in 13 patients, stable disease in 5 patients, complete response in 1 patient and progressive disease in 8 patients. Subsequent treatment with immunotherapy was not associated with increased SLP or OS in our study.

      Conclusion

      Our experience suggests that the efficacy of nintedanib-docetaxel treatment is not modified by the treatment of previous or subsequent with immunotherapy.

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      P2.01-81 - Predictive Factors of Survival in Patients Treated with Nintedanib: A Multicenter Retrospective Spanish Study (Now Available) (ID 2275)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Nintedanib is a triple angiokinase inhibitor that blocks the proangiogenic pathways mediated by vascular endothelial growth factor receptors, platelet-derived growth factor receptors and fibroblast growth factor receptors. Nintedanib in combination with docetaxel is indicated for adults with adenocarcinoma metastatic lung cancer after chemotherapy. Although, as in other antiangiogenic therapies, we do not have a predictive response marker. The aim of this study is to analyze probably factors that influence in the response to the nintedanib-docetaxel scheme.

      Method

      We conducted a retrospective multicenter study, which included all patients with non-small cell lung cancer who received nintedanib with docetaxel in second or third line of treatment. Explorative analyses were conducted according to therapy antiangiogenic previous, status PDL1, nintedanib or docetaxel dose adjustment and time to treatment fail in previous line (> 9 months or < 9 months) , age, sex and smoking.

      Result

      We enrolled 124 patients from 10 different Spanish centers. Progression free-survival was 4,1 months and the overall survival was 26,9 months. Of the factors studied, only the dose adjustment of docetaxel during treatment (5,7 months vs 2,7 months, p<0,05) and the dose adjustment of nintedanib ( 7,2 months vs 4,7 months, p<0,05 ) were associated with an increase in PFS. The dose adjustment level of nintedanib (100 mg vs 150 mg twice) did not reach statistical significance. The only factors that achieved statistical significance in overall survival were progression to the first line> 9 month (36,5 months vs 19,3 months, p <0.05) and the dose adjustment of nintedanib (37 months vs 22 months, p < 0.05). Therapy antiangiogenic previous, status PDL1, age, sex and smoking did not increase survival.

      Conclusion

      In our study, nintedanib- docetaxel concluded significant OS benefits in adenocarcinoma lung cancer patients with time to relapse to first line >9 months and in patients with dose adjustment during treatment. Further studies are needed to verify this data.

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      P2.01-98 - Neutrophil-Platelet Score (NPS), a Predictive Systemic Inflammation Score for Pembrolizumab in First Line of Advanced NSCLC Patients (ID 2711)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract

      Background

      Systemic inflammation response can be characterized by changes of peripheral blood cell amounts. Several blood cell-based scores have been found to have prognostic value in some tumors treated with ICI. Neutrophil-platelet score (NPS) is a systemic inflammation-based score characterizing 3 prognostic groups: good (0), neutrophils <=7500 and platelets <=400000; intermediate (1), neutrophils >7500 or platelets >400000; poor (2), neutrophils >7500 and platelets >400000). It has never been evaluated as prognostic biomarker in first line treatment setting of non-small-cell lung cancer (NSCLC) patients treated with pembrolizumab.

      Method

      This is a multicenter retrospective study with the aim to evaluate prognostic value of NPS in patients with advanced NSCLC and high PD-L1 expression treated with pembrolizumab monotherapy between September 2016 and March 2019. Clinical data were contributed by 12 medical centers in Spain. Primary endpoint was association of NPS with overall survival (OS).

      Result

      121 patients were evaluated. Median age was 68 years (38-88). 90 (74,4%) were male and 90 (74,4%) had PS1. Predominant histologies were adenocarcinoma (68,6%) and squamous-cell carcinoma (23,1%). Median number of cycles was 7 (1-33). Median follow-up: 6,5 months. Most were current or former smokers (95,9%). Only 1 patient had driver mutation (ALK rearrangement). 66,9% had 2 or more metastatic locations, 18,2% had central nervous system (CNS) disease, 17,4% liver metastasis, and 41,3% bone metastasis. Response rate was 40,4% according to RECISTv1.1 criteria. 11% had hyperprogression and 7,2% pseudoprogression. Estimated 12-month-OS was 62% (95%CI: 49.1%-72.5%) and estimated 12-month-PFS was 44.2% (95%CI: 31.1%-56.5%). Higher NPS was associated with poor PFS: NPS1 HR 1,23 (95%CI, 0,61-2,46), p=0,56; NPS2 HR 3,56 (95%CI, 1,61-7,86), p=0,002. NPS was not associated with disease control rate (DCR) or overall response rate (ORR).

      captura de pantalla 2019-04-10 a las 23.42.03.png

      Conclusion

      NPS predicted OS and PFS in advanced NSCLC patients with high PD-L1 expression treated with first line pembrolizumab monotherapy. NPS2 subgroup has an especially bad prognosis in spite of high PD-L1 expression and frontline treatment with pembrolizumab. These results need to be validated in prospective studies.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-33 - ctDNA Levels Significantly Predicts Survival in NSCLC Patients with an EGFR Activating Mutation (ID 2016)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract

      Background

      Circulating tumor DNA (ctDNA) have been shown to be useful for non-invasive biomarker testing in non-small cell lung cancer (NSCLC). In addition, there is growing evidence supporting that ctDNA levels can be useful for tumor response to treatment monitoring. Nevertheless, data from large prospective clinical longitudinal studies still limited.

      Method

      300 plasma samples from 100 advanced NSCLC patients, with tumors harboring an EGFR activating mutation and treated with a first line tyrosine Kinase inhibitor were analyzed. Samples were collected before the start of treatment, at first follow up evaluation, at 7 month and at disease progression. ctDNA was analyzed by dPCR.

      Result

      Median follow up was 11.3 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, afatinib or gefitinib). Patients harboring a deletion in exon 19 or a mutation in exon 21 exhibited better survival than those with an insertion in exon 20 (P<0.001). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. ctDNA levels before the start of the treatment did not significantly predict survival, although a tendency was observed, with patients with high levels of ctDNA showing poorer outcome. On the contrary, patients in which the EGFR sensitizing mutation was undetectable at first follow up had a markedly better PFS and OS (HR=2.7; 95IC= 1.4-5.5 and HR= 5.5 95IC: 1.8-17 respectively). In the same way, patients in which the EGFR sensitizing mutation remained negative at 7months had a significantly increased PFS (HR: 2.8; 95IC: 1.2-6.6). None of the patients with undetectable levels at 7 months has deceased.

      Conclusion

      ctDNA levels is of prognostic significance in EGFR positive NSCLC patients with advance disease and can be useful to monitor treatment outcome

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-10 - Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients (ID 1466)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described peripheral blood immune cells parameters as biomarkers of response to immunotherapy. In our study, we described the effect of neo-adjuvant chemo-immunotherapy treatment in Complete Blood Count (CBC) and Peripheral Blood Mononuclear Cells (PBMCs) phenotype, as well as, the association of these parameters with the degree of pathological response.

      Method

      Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), major response (<10% viable tumour) and incomplete response (>10% viable tumour, pIR). Wilcoxon and Mann-Whitney U statistic test were used to evaluate differences between pre and post treatment and between pathological responses groups respectively.

      Result

      From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers of Leucocytes, Eosinophil, Monocytes, Neutrophils, Haemoglobin and Platelets from hemograms were significantly reduced after neo-adjuvant treatment. However, no changes were observed for Lymphocytes, Basophils, LDH levels or the Lung Immune Prognostic Index (LIPI). Additionally, post-treatment Neutrophil-to-Lymphocyte (NLR), Myeloid-to-Lymphoid lineage (M:L) and Platelets-to-Lymphocytes (PLR) ratios were decreased. Remarkably, from all the CBC absolute numbers and ratios, only PLR variation showed differences between pCR and pIR.

      On the other hand, percentages of PBMCs (T cells, B cells, NK cells and macrophages) did not vary after neo-adjuvant treatment, however activation of CD4 T cells and NK cells as well as PD-1 receptor expression on immune cells were downregulated after neo-adjuvant chemo-immunotherapy. Interestingly, these variations correlate with pCR.

      Conclusion

      In our study, PLR, PD-1 expression, CD4 T cells and NK cells activation are predictive biomarkers of response to treatment. Thus, a higher decrease on PLR post neo-adjuvant treatment is associated to pCR. Moreover, a decrease of PD-1 expression in CD4, CD8 and NK cells, as well as, a reduction of CD4 T cells and NK cells activation after neo-adjuvant treatment, are associated to pCR.

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    P2.10 - Prevention and Tobacco Control (ID 176)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Prevention and Tobacco Control
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.10-02 - Smoking Habit in Lung Cancer in Spain   (ID 732)

      10:15 - 18:15  |  Author(s): Javier De Castro Carpeno

      • Abstract
      • Slides

      Background

      Tobacco is the leading cause of lung cancer. The fight against the smoking habit is essential and should be continuous, to detect the national situation that makes it possible to design health care policies against this consumption. To do so, the Grupo Español de Cáncer de Pulmón (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR).

      Method

      The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study.

      Result

      We collected data from 6,600 patients diagnosed of lung cancer from 58 different Spanish hospital sites.

      A total of 3,039 patients were former smokers (46%), 2,611 were active smokers (39%) and only 866 (12%) patients stated to be non-smokers; the status in 2% is unknown. If we make a comparison by gender regarding the presence of this habit, large differences (p-valor < 0.001) are observed, with a greater number of non-smokers in women (37 % vs. 4.5% in males), while the percentage of former smokers is much higher in the males (53.4% vs. 27.9% in women) and a minor difference in active smokers (42.1% vs. 34.4% in women).

      Significant differences were observed in the study on the distribution of the smoking habit by gender and year of diagnosis. An increase is also observed in the last two years regarding the percentage of patients who were active smoked, both for the total population as well as for each one of the two genders separately. The increase is greater among the women and, also, the number of women who are active smokers is greater in recent years.

      Mean age of onset of the smoking habit is 18.2 years. Significant differences are observed between both genders (p-valor < 0.001), with a mean age of initiation of 17.9 years in the men (95%CI 17.6-18.2 years) and 19.2 years in the women (95%CI 18.5-19.8 years). Significant differences between Regional Communities were also found in the mean age at onset of the habit, with much lower levels in the Valencian Community (16.6 years) or Navarra (16.9 years) regarding other communities, such as the Region of Murcia (22.9 years) or the Balearic Islands (21.6 years)

      Conclusion

      Lung cancer in Spain is associated to tobacco consumption in 85% of the cases diagnosed. Consumption has shown an increase in both genders in recent years and is especially rapid and worrisome in women. Anti-smoking campaigns should be reactivated and the causes of the regional differences analyzed in depth

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