Scientific Program

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    PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation

    • Type: Plenary Session
    • Track: Early Stage NSCLC
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      PL 02.02 - Patient-Reported Outcomes with Durvalumab after Chemoradiation in Locally Advanced, Unresectable NSCLC: Data from PACIFIC

      08:15 - 09:45  |  Presenting Author(s): R. Hui  |  Author(s): M. Özgüroğlu, D. Daniel, D.V. Baz, S. Murakami, T. Yokoi, A. Chiappori, K.H. Lee, M. De Wit, B. Chul Cho, J.E. Gray, A. Rydén, L. Viviers, L. Poole, P.A. Dennis, S.J. Antonia

      • Abstract

      Background:
      Durvalumab, an engineered human IgG1 anti-PD-L1 mAb, demonstrated an improvement in PFS vs placebo and favorable benefit/risk profile in the Phase 3 PACIFIC study in locally advanced, unresectable NSCLC. Here we summarize patient-reported outcomes from PACIFIC.

      Method:
      In the randomized, double-blind, Phase 3 PACIFIC study (NCT02125461), patients who had previously received ≥2 cycles of platinum-based concurrent chemotherapy with definitive dose radiation without disease progression were randomized (2:1) to durvalumab 10 mg/kg i.v. q2w or placebo for up to 12 months. Secondary endpoints included evaluation of symptoms, function and global health status/QoL using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 questionnaire and its lung cancer module, QLQ-LC13. Patients completed the questionnaires at baseline, Week 4, Week 8, q8w until Week 48, then q12w until disease progression. Changes from baseline for key symptoms were analyzed using a mixed model for repeated measures (MMRM). Time to deterioration (TTD) and odds of improvement were analyzed. Deterioration or improvement was defined as a change in score from baseline ≥10. Hazard ratios (HR) were calculated using a stratified log-rank test and odds ratios (OR) using logistic regression.

      Result:
      Compliance with completing the questionnaires was high in both durvalumab (n=476) and placebo (n=237) groups (>80% up to Week 48). There were no differences between groups at baseline in symptoms, function or global health status/QoL. MMRM analysis showed no statistically significant differences between treatment groups in adjusted mean changes from baseline (average over 12 months) in the prespecified symptoms of dyspnea, cough, chest pain, fatigue and appetite loss, and for global health status/QoL and physical functioning. Clinically relevant improvements from baseline were observed throughout the study in both durvalumab and placebo groups for dysphagia (mean [SD] change at Week 48, −14.2 [26.1] and −14.8 [25.3], respectively) and alopecia (−22.1 [33.0] and −21.4 [29.5]). There were no differences in median TTD between groups except ‘other pain’ (9.2 months with durvalumab vs 5.6 months with placebo [HR 0.72; 95%CI 0.58, 0.89]). The only difference in improvement rates between groups was for appetite loss (26.1% improvement rate with durvalumab vs 24.9% with placebo [OR 1.72; 95%CI 1.04, 2.85]). Other symptoms, function and health-related QoL remained stable throughout with no between-group differences in TTD or improvement rates.

      Conclusion:
      Durvalumab treatment did not worsen symptoms, function or health-related QoL. Clinically relevant improvement in alopecia and dysphagia with durvalumab and placebo was likely due to resolution of toxicities related to prior chemoradiation.

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    P2.02 - Biology/Pathology

    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Moderators:
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      P2.02-011 - Clinical and Molecular Features of Lung Cancers with Increased FGFR1 mRNA and/or Gene Copy Number

      09:30 - 16:00  |  Presenting Author(s): Terry L. Ng  |  Author(s): Hui Yu, E. York, S. Leedy, D. Gao, L. Heasley, Fred R. Hirsch, D. Ross Camidge

      • Abstract

      Background:
      Lung cancer cell line data suggest FGFR1 status defined by FGFR1 mRNA levels and FGFR1 gene copy number can predict sensitivity to FGFR tyrosine kinase inhibitors (TKIs).

      Method:
      A phase II biomarker preselected trial of ponatinib, an FGFR1, FGFR2, and FGFR4 targeted TKI was designed. Patients with metastatic EGFR- and ALK-negative lung cancers (both NSCLC and SCLC) were pre-screened for FGFR1 mRNA levels by in-situ hybridization (ISH) and FGFR1 gene copy number by silver in-situ hybridization (SISH). Positivity criteria for ISH were defined as a score of 3 (Dot clusters seen in 1 to <10% tumor cells; otherwise >10 dots/cell in ≥ 10% tumor cells), or 4 (Dot clusters seen in ≥ 10% of tumor cells). Positivity for SISH was defined as an average of ≥ 4 FGFR1 signal clusters/nucleus or FGFR1/CEN8 ratio ≥ 2.0. Clinical factors including sex, histology, age and sites of metastases at diagnosis of stage IV disease, smoking status, status of other known molecular drivers, and response to initial platinum-doublet therapy for stage IV disease were collected.

      Result:
      From 11/2013 to 05/2017, the study has pre-screened 163 patient samples for FGFR1 ISH and SISH. Thirty-eight (23.3%) had insufficient tissue; four had incomplete clinical or FGFR1 information. Clinical variables according to FGFR1 ISH/SISH status (n=121) are summarized in Table 1. Impact of alternate positivity cut-points, outcomes of patients treated with ponatinib and survival analysis according to ISH/SISH subgroups will be presented. Figure 1



      Conclusion:
      Although the numbers were small, the FGFR1 ISH+/SISH+ subgroup had a greater percentage small cell histology, liver metastases at diagnosis and male sex compared to other FGFR1 subgroups. FGFR1 ISH and/or SISH positivity can overlap with other known oncogenic drivers suggesting that the initial cut-points for FGFR1 positivity used may be too low to identify a true FGFR1 addicted state.

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      P2.02-018 - Genomic Profiling of Driver Gene Mutations in 498 Chinese NSCLC Patients

      09:30 - 16:00  |  Presenting Author(s): Minghui Wang  |  Author(s): Mingwu Chen, Y. Shi, Q. Guo, Y. Shang, J. Hu, L. Dai, M. Yao, H. Chen, J. Hu, J. Yao, A. Wang, G. Chirn, K. Wang

      • Abstract

      Background:
      Identifying genomic alterations of actionable driver genes in non-small cell lung cancer (NSCLC) such as EGFR, ALK, ROS1 has been used as important evidences for firstline treatments. Patients with driver mutations received matched target drugs could have significantly longer progression free and overall survival.

      Method:
      FFPE tumor samples of 498 Chinese NSCLC patients including 279 males (56%) and 219 females (44%) with a median age of 60 were collected for next-generation sequencing (NGS)-based multi genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, and gene rearrangement and fusions in selected genes were assessed.

      Result:
      Different histological subtypes of adenocarcinoma (417/498, 83.7%), squamous carcinoma (68/498, 13.7%), mixed carcinoma (6/498, 1.2%) and large cell carcinoma (7/498, 1.4%) were included in the Chinese NSCLC cohort. The top ranked genomic alterations in driver genes were EGFR (47.8%), KRAS (10.0%), ALK fusions (8.2%), PIK3CA (7.0%), HER2 (6.2 %), PTEN (3.6%), BRAF (2.6%), MET (3.6%), RET fusions (1.6%), and ROS1 fusions (0.8%), which counts up to 86.9% of the 498 patients with at least one driver mutation. In addition to common driver mutations, rare mutation types such as EGFR-KDD, EGFR-RAD51, AMOTL2-NTRK1 and KIF13A-RET were also detected by deep sequencing assay.

      Conclusion:
      Our study revealed the landscape of driver gene mutations in 498 Chinese NSCLC patients. Comparing to the largest public NSCLC cohort from Foundation Medicine, mostly Western populations (N=6823, PMID: 27151654), we identified similar frequencies of some driver genes, but more ALK fusions (8.2% vs 3.9%), EGFR mutations (47.8% vs 20.0%) as druggable target genes, and less KRAS mutations (10.0% vs 32.0%) consistent with reported results. Totally 78.7% of the Chinese patietns harbored at least one mutaiton in the 8 core driver genes including EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, or KRAS (vs. 71% in the FMI cohort). Our findings demonstrated that genomic profiling of driver genes in NSCLC showed significant differences among racial or ethnic groups, which indicated different treatment options between Eastern and Western populations.

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      P2.02-033 - The Association of PD-L1 Expression with Clinical Characteristics and EGFR and ALK Status in Lung Adenocarcinoma

      09:30 - 16:00  |  Presenting Author(s): Jinghui Wang  |  Author(s): S. Wu, Xiaohua Shi, Y. Liu, X. Zeng, L. Zhou

      • Abstract

      Background:
      Programmed cell death-1 (PD-1) inhibitor is one of important medicines of immunotherapy for cancers. Programmed cell death ligand-1 (PD-L1) expression is a valuable predictor for selection of patients by PD-1 inhibitors therapy. However, the correlation of PD-L1 expression with clinicopathologic features, EGFR and ALK status, and prognosis of lung adenocarcinoma remain controversial.

      Method:
      421 lung adenocarcinoma patients with identified EGFR and ALK status in tumor tissues were enrolled. Using tissue microarrays, PD-L1 expression was evaluated using clone SP263 antibody by immunohistochemistry (IHC) on Ventana Benchmark automated staining system. The association of PD-L1 expression with clinicopathologic characteristics, EGFR and ALK status and prognosis of lung adenocarcinoma were analysed.

      Result:
      A total of 404 patients were available for evaluation. The positve incidence of PD-L1 expression was 22.5% (91/404) (using a cutoff of ≥ 25%). Multivariate Logistic regression analysis showed PD-L1 expression was associated with advanced stage (ORR 2.190, 95% CI 1.313-3.651, P = 0.003), solid predominant subtype (ORR 3.594, 95% CI 1.826-7.073, P < 0.001), and wild-type epidermal growth factor receptor (EGFR) (ORR 1.895, 95% CI 1.091-3.291, P = 0.023), while it was not associated with ALK rearrangement. In multivariate analysis for OS by Cox hazard proportion model, patients with early stage (HR 2.495, 95% CI 2.003-3.106, P < 0.001) and EGFR mutations (HR 1.635, 95% CI 1.310-2.040, P < 0.001) had a significantly longer survival, while PD-L1 expression was not associated with OS of patients with lung adenocarcinoma (HR 0.847, 95% CI 0.655-1.094, P = 0.203).

      Conclusion:
      Positive PD-L1 expression in lung adenocarcinoma tissues was significantly associated with tumor advanced stage, solid predominant subtype, and wild-type EGFR, however, PD-L1 expression may not be a predictor of OS for patients with lung adenocarcinoma.

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    P2.04 - Clinical Design, Statistics and Clinical Trials

    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Moderators:
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      P2.04-011 - The Using of LungCare Electromagnetic Navigated Bronchoscopy System in Lung Lesions, a New Project in China

      09:30 - 16:00  |  Presenting Author(s): Baohui Han  |  Author(s): S. Jiayuan, X. Zheng

      • Abstract

      Background:
      With the application of low dose computed tomography in screening lung cancer for high-risk population, more peripheral pulmonary lesions are found which need to be diagnosed or treated. Traditional methods include transthoracic needle aspiration (TTNA) or transbronchial lung biopsy (TBLB) are not recommended nowadays because of its low diagnostic rate, more complications and high radiation dose for patients. Moreover, they lack real-time navigation system for guiding bronchoscope to the distal lesion where traditional methods hardly reach and highly depends on operators with knowledge of CT scans. Electromagnetic navigated bronchoscopy (ENB) has proven to be a novel technology, including electromagnetic tracking, virtual bronchoscopic navigation and CT reconstruction technologies. Only two commercial ENB systems have been approved by FDA in the United States. And more than 1,000 medical institutions have been equipped with ENB in Europe and the United States. As of the end of June 2016, more than 10 imported ENB systems were installed in China.

      Method:
      This project has been supported by the ministry of science and technology of the People’s Republic of China in 2017(2017YFC0112700). This project will utilize the domestic LungCare ENB system and its improved version to carry out five innovative sub-projects. These projects will cover all the issues of ENB on the early peripheral lung cancers (Stage IA), including the diagnosis, localization and treatment.

      Result:
      First, the project will utilize the CFDA approved LungCare ENB system to perform a large, prospective, multicenter, randomized study, which aims to enroll up to total 1362 consecutive subjects presenting for evaluation (diagnosis, localization and treatment) of lung lesions utilizing the ENB procedure at up to 3 clinical sites. Second, LungCare ENB system will upgrade their products and develop two new navigation systems including the transthoracic electromagnetic navigation system(TTEN) and the video assisted thoracoscopic surgery electromagnetic navigation system (VATS-EN). Two clinical studies will be performed in 3 clinical sites individually.

      Conclusion:
      LungCare ENB total solution including ENB, TTEN and VATS-EN, will extend their electromagnetic navigation system of the single use from the bronchus to the thoracic wall, and even through the thoracoscope. The value of the project will form the whole-lung electromagnetic navigation system and focus on the accurate diagnose, localization and treatment of early peripheral lung cancer.

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    P2.14 - Radiotherapy

    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Moderators:
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      P2.14-004 - Comparable Local Controls after Twice-Daily and Once-Daily Chest Radiotherapy in Extensive Stage Small Cell Lung Cancer

      09:30 - 16:00  |  Presenting Author(s): Bo Qiu  |  Author(s): Q. Li, W. Xie, Z. Hui, B. Wang, Y. Liang, J. Guo, Y. Zhou, M. Zhu, W. Shen, R. Duan, L. Chen, Li Zhang, H. Long, Hui Liu

      • Abstract

      Background:
      The optimal radiation schedule for small cell lung cancer (SCLC) has not yet fully established. This study was designed to compare the clinical outcomes between twice- and once-daily radiotherapy in the treatment of SCLC.

      Method:
      One hundred and twenty-four consecutive patients diagnosed with extensive stage SCLC and treated with chemoradiotherapy were retrospectively reviewed. Either twice-daily hyper-fractionated irradiation (45 Gy/30 fractions/BID), or alternative schedules, including hypo-fractionated (45 Gy/15 fractions/QD) or conventionally fractionated (50 Gy/25 fractions/QD or 60 Gy/30 fractions/QD) radiation was delivered, with etoposide and platinum prescribed concurrently or sequentially. Local controls and overall survivals were calculated and compared between twice- and once-daily schedules based on Kaplan-Meier method. Toxicities were record according to Common Terminology Criteria Adverse Events.

      Result:
      There were 67 and 57 patients received twice- and once-daily chest radiotherapy, respectively. With a median follow-up of 27 and 24 months, the local control rates were reported 64.2% and 63.2%. The 2-year estimated local progression-free survival rates were similar (61.6% vs 61.0%, p=0.90). Progressive disease identified three months after radiotherapy was correlated to increased local failure (p=0.026). There was no difference between the incidences of grade 3-4 toxicities between twice- and once-daily schedules (23.9% vs 12.3%, p=0.16).

      Conclusion:
      Either twice- (45 Gy/30 fractions/BID) or once-daily (45 Gy/15 fractions/QD, 50 Gy/25 fractions/QD, 60 Gy/30 fractions/QD) radiation schedule could be considered in the treatment of SCLC, resulting in comparable local control and toxicities.

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    PR 03 - Press Conference

    • 10:00 - 10:45
    • 10/17/2017
    • Location: Room 418
    • Type: Press Conference
    • Track:
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      PR 03.04 - Patient-Reported Outcomes with Durvalumab after Chemoradiation in Locally Advanced, Unresectable NSCLC: Data from PACIFIC

      10:00 - 10:45  |  Presenting Author(s): R. Hui

      • Abstract

      Abstract not provided

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    MA 13 - New Insights of Diagnosis and Update of Treatment

    • Type: Mini Oral
    • Track: Early Stage NSCLC
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      MA 13.02 - Comprehensive Genetic Analysis Related to  PD-L1 Expression in Early-stage Lung Squamous Cell Carcinoma

      15:45 - 17:30  |  Presenting Author(s): Hui Yu  |  Author(s): Z. Chen, K. Ballman, M. Watson, Ramaswamy Govindan, D. Beer, Raphael Bueno, L. Chirieac, M.H. Chui, W.A. Franklin, David R. Gandara, C. Genova, M. Joshi, D.T. Merrick, W.G. Richards, C.J. Rivard, Frances A Shepherd, T. Sporn, Ming Sound Tsao, K. Brovsky, A.V. Bokhoven, David Harpole, Fred R. Hirsch

      • Abstract

      Background:
      Recently, anti PD-1/PD-L1 immunotherapies have yielded promising outcomes in advanced squamous NSCLC. Several studies have suggested that tumor PD-L1 protein expression status might correlate with outcome and response to treatment. The aim of this study is to identify mRNA gene signatures and microRNAs associated with tumor PD-L1 expression in early-stage lung squamous cell carcinoma (SCC).

      Method:
      Early stage (I-II) SCC resected patient tumors were collected from 6 cancer centers as part of the SPECS II program. Gene expression profiling was performed on the specimens. PD-L1 protein expression was evaluated by immunohistochemistry on SCC FFPE tissue using the Dako 22C3 PD-L1 antibody. The tumor proportion score (TPS) for PD-L1 protein expression was compared with comprehensive clinicopathological, mRNA and miRNA data.

      Result:
      The prevalence of PD-L1 expression in this cohort of 255 Stage I-II SCC patients was 46.7% with a TPS cutoff of ≥ 1%, and 9.8% with a cutoff of ≥ 50%. Among 202 cases with available clinical and expression data, no significant association was observed between PD-L1 expression and clinical outcome. We identified a 12-gene signature from mRNA microarray using the Minimax Concave Penalty (MCP) regression method with an AUC of 0.92 at ≥ 5% TPS cutoff. A subset of 138 miRNAs was shown to be significantly differentially expressed between PD-L1 positive and PD-L1 negative groups at false discovery rate (FDR) of 0.05 with TPS cutoffs of ≥ 1%, ≥ 5% and ≥ 10%. No miRNAs were found to be significantly differentially expressed between the groups using a TPS cutoff of ≥ 50%. Gene Set Enrichment Analysis (GSEA) identified two pathways with gene sets that were significantly enriched (FDR < 0.05) in the PD-L1 negative group. No significant association was found between tumor mutation burden and PD-L1 expression level.

      Conclusion:
      PD-L1 expression prevalence is lower in early-stage lung SCC than in advanced NSCLC. No significant association was found between PD-L1 expression and prognosis in this cohort. Both mRNA gene signatures and miRNAs were identified to be predictive of PD-L1 expression. Through GSEA, two distinct gene sets were identified with expression correlated to PD-L1, one comprising genes related to ovary and another related to collagens and extracellular matrix (ECM). No significant association was found between tumor mutation burden and PD-L1 expression level. Following validation, these predictive signatures could be used to select patients with positive PD-L1 expression who may benefit from immunotherapy.

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    MA 14 - Diagnostic Radiology, Staging and Screening for Lung Cancer I

    • Type: Mini Oral
    • Track: Radiology/Staging/Screening
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      MA 14.07 - Randomized Lung Cancer Screening with Low-Dose CT in China: A Specific Risk-Based Screening for Chinese Population

      15:45 - 17:30  |  Presenting Author(s): Baohui Han  |  Author(s): H. Wang, J. Teng, J. Ye, Q. Chen, Y. Zhang, W. Yang, F. Qian

      • Abstract

      Background:
      The purpose of the present study was to investigate whether low-dose computed tomography (LDCT) screening is capable of enhancing the detection rate of early-stage lung cancer and reducing lung cancer mortality rate in China, thus determining the appropriate duration of screening and identifying additional risk factors for lung cancers in Chinese population.

      Method:
      A randomized lung cancer screening study was performed with participants aged 45 to 70 years old who had at least one high-risk factor as follows: 1) a history of cigarette smoking ≥20 pack-years; former smokers who had quit within the past 15 years; 2) cancer history in immediate family members; 3) personal cancer history; 4) professional exposure to carcinogens (asbestos, dust or radiation); 5) long history of passive smoking; or 6) long-term exposure to cooking oil fumes. Participants were randomly assigned to a screening group with alternating years of LDCT screening (R1, R2) or a control group with biennial questionnaire inquiries.

      Result:
      A total of 6657 eligible participants were enrolled, 3145 participants were assigned to the control group and 3512 were assigned to the baseline LDCT screening (R1) group. 1516 participants (43.2%) underwent the second round of LDCT screening (R2) in the alternate year. At R1 and R2 rounds, 19.6% and 24.0% participants showed non-calcified nodules ≥4 mm on LDCT images. Among these, lung cancer was diagnosed in 44 participants (1.3%) at R1, 12 (0.8%) at R2, and 10 (0.3%) in the control group through either biopsy or cytologic analysis. The proportions of early-stage (0 to I) lung cancer were 97.7% at R1, 91.7% at R2 and 20% in the control group, respectively. At R1, the sensitivity of LDCT for lung cancer screening was 97.7%, the specificity was 76.8%, the positive predictive value was 5.1%, and the negative predictive value (NPV) was 99.9%; at R2, both the sensitivity and the negative predictive value increased to 100%. Two cases of lung cancer-specific deaths occurred in the control group, but no death occurred in the LDCT group.

      Conclusion:
      Compared to usual care, the two biennial screenings with LDCT led to a 77.7% increase at R1 and 71.7% at R2 in detecting early-stage lung cancer and a 20% decrease in lung cancer mortality. Biennial screening may be at least as efficient as annual screening in terms of detecting rate, sensitivity and NPV. This study provides insights about the non-smoking related risk factors of lung cancer in the Chinese population.