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Tony S. Mok

Moderator of

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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 20
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      JCSE01.02 - Necessity for Early Detection in Lung Cancer and Initial Attempts for Early Detection (ID 11395)

      08:00 - 08:20  |  Presenting Author(s): Annette Maree McWilliams

      • Abstract

      Abstract not provided

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      JCSE01.03 - CT Screening for Early Detection (NLST, UKLS, NELSON, ITALUNG, DANTE, Others) (ID 11396)

      08:20 - 08:40  |  Presenting Author(s): Matthijs Oudkerk

      • Abstract

      Abstract not provided

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      JCSE01.04 - Risk Modeling for the Early Detection of Tin Miner Lung Cancer in China (ID 11397)

      08:40 - 09:00  |  Presenting Author(s): You-lin 13910410711 Qiao

      • Abstract

      Abstract

      Result of National Lung Cancer Screening Program has demonstrated a 20% reduced lung cancer mortality with low-dose computed tomography among current or former smokers with a smoking history of 30 or more pack-years[1]. Selecting high risk population for LDCT screening is a key issue for lung cancer screening. Many studies have suggested that lung cancer risk model which incorporating these factors can be more accurate to identify high risk individuals suitable for LDCT screening than the NLST criteria[2]. Thus, more precise evaluation of association between these factors are warranted to developing lung cancer risk models.

      In this study, we developed and internal validated a lung cancer risk model with data of a occupational screening cohort in Yunnan, China with the aim to exploring potential improvement of yield of lung cancer screening with Chest X-ray and Sputum cytology due to the improved risk stratification. This study was a prospective occupational cohort study among tin miners from Yunnan Tin Corporation (YTC) initiated in 1992[3]. Participants were tin miners aged 40 or over and had at least 10 years of underground work or smelting history. Participants also had received annual lung screening from 1992 to 1999, and were annually followed up through December 31, 2001. Previous studies suggested that age, education level, smoking, occupational radon and arsenic exposure, prior chronic bronchitis were risk factors of lung cancer risk in this cohort[4-6]. During the study period, a total of 443 lung cancer deaths were confirmed among 9295 participants. To reduce the potential information bias, 69 lung cancer death with 1 year since enrollment were not included into the analysis.

      To stratified those with higher lung cancer risk, we increased the age criteria from 40 to 50 years old(model 0), then further developed three risk prediction models with multivariate logistic regression respectively, and the predicted probability of lung cancer death for each participants were also calculated based on logistic regression model respectively(table1). The goodness of fit, discrimination and calibration ability of the model performance were evaluated with -2log likelihood, area under the receiver operator characteristic curve (AUC) (C-index) and Hosmer-Lemeshow test. We found that the model incorporated age, gender, smoking, educational prior chronic bronchitis, occupational radon and arsenic had the best discrimination performance with area under ROC as of 0.821(95%CI:0.805-0.836) (figure1a). The calibration performance of this model was also good(Hosmer–Lemeshow type χ2=5.413,p=0.773)(figure1b). The areas under ROC curve of model 2 and model 3 were significantly better than those of model1 and model 0(all p<0.001), however, no difference was found between model 2 and model 3. Besides, Bootstrapping techniques were used for internal validation of the model 3 to Correct for this overfit or optimism, and discrimination C-statistic from C-statics was the same to the original data.

      We stratified the participants into 4 quintiles for the predicted risk of death from lung cancer. The cumulative lung cancer death rate from quintile 1 with lowest risk to quintile 4 having the highest risk increased from 11.51, 47.66, 625.41 to 1732.37 per 105 person-years, while only 2.5% of all lung cancer deaths were in quintile 1 and 2. Similarly, in 210 screen-detected lung cancer deaths, the proportion in quintile 1 and 2 was only 2.4%.

      In conclusion, we have developed and internal validated a lung cancer risk model based on personal and occupation covariates in this occupational population, and this model showed good accuracy for the identification of lung cancer and might assist in identifying individuals at high risk of developing lung cancer in lung cancer screening in this occupational cohort.

      [1] Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011. 365(5): 395-409.

      [2] Tammemägi MC. Application of risk prediction models to lung cancer screening: a review. J Thorac Imaging. 2015. 30(2): 88-100.

      [3] Qiao YL, Taylor PR, Yao SX, et al. Risk factors and early detection of lung cancer in a cohort of Chinese tin miners. Ann Epidemiol. 1997. 7(8): 533-41.

      [4] Lubin JH, Qiao YL, Taylor PR, et al. Quantitative evaluation of the radon and lung cancer association in a case control study of Chinese tin miners. Cancer Res. 1990. 50(1): 174-80.

      [5] Fan YG, Jiang Y, Chang RS, et al. Prior lung disease and lung cancer risk in an occupational-based cohort in Yunnan, China. Lung Cancer. 2011. 72(2): 258-63.

      [6] Yao SX, Lubin JH, Qiao YL, et al. Exposure to radon progeny, tobacco use and lung cancer in a case-control study in southern China. Radiat Res. 1994. 138(3): 326-36.

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      JCSE01.05 - Biomarkers and Liquid Biopsy for Early Detection of Lung Cancer (ID 11398)

      09:00 - 09:20  |  Presenting Author(s): K.C. Allen Chan

      • Abstract

      Abstract

      The analysis of circulating DNA released by tumor cells, frequently known as liquid biopsy, provides a convenient and noninvasive way for the assessment of cancers. The most common application of liquid biopsy is to guide the choice of treatment in lung cancers. The detection of EGFR mutations in the plasma of patients with advanced lung cancers is useful for predicting the response to EGFR TKI treatment. Because of its noninvasive nature and quick turn-around time, liquid biopsy has been proposed to be a first line investigation for the assessment of EGFR mutational status. Another potential application of liquid biopsy is for the screening of early cancers. However, there is a lack of information regarding the biological feasibility of this approach as it is unclear if a small tumor would release sufficiently large amount of DNA into the circulation to allow early detection of the cancer. In this regard, we used nasopharyngeal cancer (NPC) as a model to address this biological question. As NPC is closely related to Epstein-Barr virus infection, we developed plasma EBV DNA as a marker for NPC. From 2013 to 2016, we screened over 20,000 asymptomatic men for NPC using a sensitive plasma EBV DNA assay. Subjects with positive test results were further investigated with nasal endoscopy and MRI. Through this arrangement, we identified 34 cases of NPC and almost half of them had stage I disease. Compared with historical cohorts, patients identified by screening had much improved progression-free survivial with a hazard ratio of 0.1. This study clearly demonstrates that a small early cancer can release sufficiently large amount of DNA into the circulation to allow sensitive detection by liquid biopsy. To apply these results to non-viral-associated cancers, we developed a generic cancer test based on copy number aberrations and altered methylation in plasma DNA. This test successfully detect various types of cancers, including lung cancer.

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      JCSE01.06 - Incorporating Artificial Intelligence for Early Detection of Lung Cancer (ID 11399)

      09:20 - 09:40  |  Presenting Author(s): Jie Hu

      • Abstract

      Abstract not provided

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      JCSE01.09 - Cluster Trial: Ph2 Biomarker-Integrated Study of Single Agent Alpelisib, Capmatinib, Ceritinib and Binimetinib in advNSCLC (ID 11678)

      10:15 - 10:25  |  Presenting Author(s): Qing Zhou  |  Author(s): Yi-Long Wu, Xu-Chao Zhang, Hai-Yan Tu, Bin Gan, Bin-Chao Wang, Chong-Rui Xu, Hua-Jun Chen, Ming-ying Zheng, Zhen Wang, Xiao-Yan Bai, Yue-Li Sun, Andrea Myers, Xueting Lv, Yajnaseni Chakraborti, Sylvia Zhao, Jin -Ji Yang

      • Abstract
      • Slides

      Background
      Several genetically altered signaling pathways have been profiled in NSCLC, enabling advanced management of NSCLC using targeted therapies. This study investigated the therapeutic spectrum of NSCLC with uncommon molecular alterations by allocating patients to treatment arms based on molecular aberrations; targeted therapies alpelisib (PI3Kαi), capmatinib (METi), ceritinib (ALKi), and binimetinib (MEKi) were evaluated.The study was based on the umbrella design. Key objectives: investigate feasibility of using one trial for different agents based on biomarker-integrated analysis, assess anti-tumor activity, characterize safety, tolerability and PK profiles of individual agents. Key eligibility criteria: age ≥18 years; ECOG PS ≤2; failed prior treatment/unsuitable for chemotherapy. Documentation of locally determined molecular alterations before treatment allocation was required (alpelisib, 350 mg QD: PIK3CA mutation/amplification; capmatinib, 400 mg BID (tablet): MET IHC overexpression/amplification; ceritinib, 750 mg QD: ALK or ROS1 rearrangement; binimetinib, 45 mg BID: KRAS, NRAS or BRAF mutation).Sixty-six patients with advNSCLC were enrolled (median age 58 years; 65.2% male: alpelisib, n=2; capmatinib, n=16; ceritinib, n=26; binimetinib, n=22). As of Feb 28, 2018, 10 patients in ceritinib and 2 in binimetinib arms were ongoing. Twenty-four patients had confirmed partial responses (36.4%): alpelisib, 0%; capmatinib, 18.8%; ceritinib, 73.1%; binimetinib, 9.1% (Figure). Longest mPFS (14.4 months) was in ceritinib arm. Among the most common treatment-related AEs: alpelisib: malaise, hyperglycemia, dysgeusia; capmatinib: nausea, anemia, peripheral edema, decreased appetite; ceritinib: diarrhea, vomiting, ALT/AST elevation; binimetinib: mouth ulceration, AST, blood CPK increased, rash. Most AEs were grade 1/2.

      abstract #1.jpg

      Objective responses/tumor shrinkage were observed in the study; highest ORR and mPFS were observed with ceritinib, although patient numbers differed between arms. All treatments were well tolerated; no new safety signals were observed. This study demonstrated the feasibility of an umbrella trial and importance of precision medicine in the management of advNSCLC with uncommon molecular alterations.

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      JCSE01.10 - A Ph3 Study of Niraparib as Maintenance Therapy in 1L Platinum Responsive Extensive Disease Small Cell Lung Cancer Patients (ID 11679)

      10:25 - 10:35  |  Presenting Author(s): Shun Lu  |  Author(s): Liyan Jiang, Xinghao Ai, Junling Li, Xiaorong Dong, Dan Zhang, Qi Liu

      • Abstract
      • Slides

      Background
      Small cell lung cancer (SCLC) accounts for 15% of lung cancer, characterized by early dissemination and rapid development of chemo-resistant disease after platinum response (60-80%). Less than 2% of extensive disease SCLC (ED-SCLC) patients survive 5 years. The bi-allelic loss or inactivation of TP53 and RB1 is common in SCLC, the poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA damage repair enzyme, is highly expressed in SCLC, and SCLC is sensitive to platinum based chemotherapy, suggesting that the defect in DNA damage repair pathways plays an important role in SCLC. ZL2306/ Niraparib is a highly selective PARP-1/2 inhibitor which was exclusively licensed for development in China by Zai Laboratory from TESARO. In SCLC PDX model, niraparib demonstrated anti-tumor activities as monotherapy. In addition, niraparib demonstrated promising tumor growth inhibition in maintenance post platinum treatment in platinum sensitive SCLC PDX models. Clinically, in phase III NOVA study, niraparib demonstrated clear clinical benefit as maintenance treatment by significantly extending progression free survival in all platinum-sensitive recurrent ovarian cancer patients regardless gBRCA or HRD status which led to the approval by FDA and EMA in ovarian cancer. It is suggested that niraparib maintenance therapy could provide potential clinical benefit in platinum responsive SCLC. ZL-2306-005 is a randomized double-blind multi-center phase 3 study to evaluate the efficacy and safety of niraparib versus placebo as maintenance therapy in ED-SCLC patients who have had responses to platinum based chemotherapy.Approximately 590 Chinese patients with histologically or cytologically confirmed ED-SCLC who have achieved either complete response or partial response to their platinum based chemotherapy to their newly diagnosed disease will be randomized (2:1) to 2 groups, receiving either ZL-2306 or placebo in ZL-2306-005 study. Patients need to complete 4 cycles of etoposide + cisplatin/ carboplatin. All patients will be stratified by gender, LDH level and history of prophylactic cranial irradiation. ZL-2306 will be started with 300mg PO QD for patients with a baseline body weight ≥77 kg and a baseline platelet count ≥150,000/μL, or 200 mg PO QD for patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL based on RADAR analysis in NOVA study. Patients will remain on treatment until disease progression or intolerable toxicity. The co-primary endpoints are PFS assessed by independent central radiologic review and OS; the secondary endpoints are PFS assessed by investigator, CFI, QoL, safety and tolerability.

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      Section not applicable

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      JCSE01.11 - Dynamic ctDNA Monitoring Revealed Novel Resistance Mechanisms and Response Predictors of Osimertinib Treatment in East Asian NSCLC Patients (ID 14716)

      10:35 - 10:45  |  Presenting Author(s): Jianhua Chang  |  Author(s): Zhihuang Hu, Dongmei Ji, Shannon Chuai, Weina Shen, Junning Cao, Jialei Wang, Xianghua Wu

      • Abstract
      • Slides

      Background

      Advanced NSCLC patients, harboring EGFR T790M, exhibit marked diversity in tumor behavior and response to AZD9291, yet a discriminable molecular profile remains elusive. In addition, although EGFRC797S was involved in 30% of AZD9291 resistance cases in Western patients, mechanisms for the rest patients remain unclear, especially for the East Asian population. We utilized circulating tumor DNA (ctDNA) profiling to conduct dynamic monitoring in patients undergoing AZD9291, thus characterizing mutational heterogeneity and genomic evolution.

      Longitudinal plasma samples were collected before, during and post of the AZD9291 treatment in Chinese NSCLC patients with acquired T790M mutation. A ctDNA panel, spanning 160KB of human genome, was used to perform capture-based targeted sequencing that comprises critical exons and introns of 168 genes. The EGFR mutation abundance and dynamic changes of allele fraction (AF) were analyzed with progression-free survival (PFS) after AZD9291 treatment.

      A total of 61 samples were collected longitudinally from 14 patients, of which 9 have experienced progressive disease (PD). Six patients exhibited a rebound of ctDNA prior to radiographic PD, suggesting the potential of ctDNA in early detection of PD. Several acquired mutations were detected with the AZD9291 resistance, including newly identified EGFR G796S, L792H/F/R/V, V802F, V843I mutations, expect for the previously reported RB1 and EGFR C797S, L718Q mutations. Patients with a higher ratio of T790M and EGFRactivating mutation at baseline had a significantly longer PFS (9.6m vs 4.5m, p=0.008). A lower ratio of EGFRactivating mutation AF compared to baseline at first follow-up was significantly correlated with a longer PFS (8.5m vs 5.0m, p=0.027). Furthermore, patients harboring other known driver mutations in addition to T790M at baseline had an inferior PFS (4.9m vs 7.8m, P=0.039).

      Several novel resistance mechanisms were identified by ctDNA monitoring in the East Asian patients treated with AZD9291. Relative AF of T790M, changes of AF after treatment and the presence of concurrent driver mutations at baseline could predict clinical benefit of AZD9291 treatment.

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      JCSE01.12 - Discussant Oral Abstracts (ID 11681)

      10:45 - 11:00  |  Presenting Author(s): Daniel S.W. Tan

      • Abstract

      Abstract not provided

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      JCSE01.13 - Discussant Poster Abstracts (ID 11682)

      11:00 - 11:15  |  Presenting Author(s): Bob T. Li

      • Abstract

      Abstract not provided

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      JCSE01.14 - Effects of Neoadjuvant Chemotherapy on the Expression of Programmed Death Ligand-1 and Tumor Infiltrating Lymphocytes in Lung Cancer Tissues (ID 14703)

      11:15 - 11:15  |  Presenting Author(s): Xu Wang  |  Author(s): Wenyu Sun, Kewei Ma

      • Abstract

      Background
      Immune checkpoints programmed death 1(PD1)and its ligand PD-L1,PD-L2 pathways can mediate negative synergistic stimulation signals.Immunotherapy combined with chemotherapy can increase the objective response rate of cancer patients,but the mechanism of combination therapy is not clear.This study aims to analyze the changes of PD-L1,PD-L2 in lung cancer tissues and the changes of TILs ( CD4+,CD8+,CD28+,and CD56+ lymphocytes ) surrounding the tumor before and after neoadjuvant chemotherapy(platinum-based),in order to provide a theoretical basis for relevant clinical studies.Tumor samples were obtained from 26 patients who confirmed primary lung cancer before and after NAC from 2009 to 2016 in the First Hospital of Jilin University. The expression of PD-L1, PD-L2 in lung cancer specimens were assessed by IHC. 5%,10%,20%,30%,50% expression thresholds were used to define PD-L1, PD-L2 positive status, respectively. Of 16 patients ( since the biopsy tissue specimens were limited, only 16 cases of biopsy and postoperative tissue specimens were collected), the expression of TILs around the tumor before and after NAC were assessed by IHC. We analyze the changes of PD-L1 and PD-L2 in lung cancer tissues before and after NAC, the correlation between the changes of PD-L1 in lung cancer tissues and tumor shrink rate, the interval from the end of NAC to operation, pathological type, gender and smoking status. Of 16 patients, the changes of TILs around the tumor before and after NAC were also evaluated. P<0.05 was considered statistically significant.

      1. When using 5%, 10%, and 20% as expression threshold to define PD-L1 positive status, PD-L1 was up-regulated after NAC (P=0.008,P=0.016,P=0.016). However, there were no obviously statistical significance about the expression of PD-L1 when using 30%, 50% expression threshold. The expression of PD-L2 were not show any statistical significance before and after NAC.

      2. Of 16 patients, the expression of CD4+, CD8+ and CD28+ lymphocytes increased after NAC (P=0.014,P=0.038,P=0.021), whereas the change of CD56+ lymphocytes was not statistical significant.

      3. There were no significant difference between the changes of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status .

      1. NAC up-regulates the expression of PD-L1 in lung cancer tissues when the expression thresholds are 5%, 10%, and 20%.

      2. NAC up-regulates the expression of CD4+, CD8+, and CD28+ lymphocytes.

      3. No correlation exists between the variation of PD-L1 and tumor shrink rate, interval from the end of NAC to operation, pathological type, gender and smoking status.

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      JCSE01.15 - Molecular Characteristics of ALK Primary Point Mutations Non-Small-Cell Lung Cancer in Chinese Patients (ID 14704)

      11:15 - 11:15  |  Presenting Author(s): Chunwei Xu  |  Author(s): Jinhuo Lai, Wenxian Wang, Quxia Zhang, Wu Zhuang, Yunjian Huang, Youcai Zhu, Yanping Chen, Gang Chen, Meiyu Fang, Tang Feng Lv, Yong Song

      • Abstract
      • Slides

      Background
      Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung cancer at 3-7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease. While the genetic locus of ALK primary point mutations NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring ALK primary point mutations.

      A total of 339 patients with non-small-cell lung cancer were recruited between July 2012 and December 2015. The status of ALK primary point mutation and other genes were detected by next generation sequencing.


      ALK gene primary point mutation rate was 8.55% (29/339) in non-small cell lung cancer, including V163L (3 patients), F921Gfs*16 (2 patients), K1416N (2 patients), A585T (2 patients), P1442Q (1 patient), A348T (1 patient), K1525E (1 patient), S737L (1 patient), P115L (1 patient), Q515E (1 patient), E314D (1 patient), R395H (1 patient), S1219F (1 patient), S341G (1 patient), P1543S (1 patient), G129V (1 patient), Q167H (1 patient), L550F (1 patient), T1012M (1 patient), D302Y (1 patient), H755Q (1 patient), H331Q (1 patient), G1474E (1 patient) and E119D (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, 27 patients with co-occurring mutations had a median OS of 20.0 months, and median OS of the 2 patients without complex mutations was 8.5 months. Statistically significant difference was found between the two groups (P=0.02). Briefly, patients with (n=8) or without (n=21) co-occurring EGFR mutations had a median OS of 24.0 months and 20.0 months respectively (P=0.73); patients with (n=21) or without (n=8) co-occurring TP53 mutations had a median OS of 20.0 months and 17.0 months respectively (P=0.83).

      EGFR and TP53 gene accompanied may have less correlation with ALK primary point mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.

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      JCSE01.16 - Positive Correlation Between Whole Genomic Copy Number Variant Scoring and the Grading System in Lung Non-Mucinous Invasive Adenocarcinoma  (ID 14705)

      11:15 - 11:15  |  Presenting Author(s): Zheng Wang  |  Author(s): Shenglei Li, Lin Zhang, Lei He, Di Cui, Chenglong Liu, Yuyan Gong, Bi Liu, Xiaoyu Li, Wang Wu, David Cram, Dongge Liu

      • Abstract
      • Slides

      Background
      Grading systems of Lung adenocarcinoma have been proposed by Sica and Kadota in stage I tumors,but the predominant architectural subtypes grading system is applicable for resection samples mostly. The correlation between the histological subtypes and grading with whole genomic copy number variation(WGCNV) is unknown, and was investigated in lung non-mucinous invasive adenocarcinoma (LNMIA) at this study.The predominant histological subtype from 58 resection specimens of LNMIA and 20 para-cancerous lung tissues were collected by laser microdissection from HE staining FrameSlides PEN-Membrane slides.7 of 58 specimens,two predominant subtypes in one cancerous nodule were collected simultaneously. Whole genome amplification followed by high-throughput sequencing was used to deteted WGCNV with the para-cancerous lung tissues as normal reference set and WGCNV was scored by a particular formula.
      abstract #1.jpgabstract #2.jpg

      The letters above the figure show the results of Chi-squared test, and same letters mean no significant difference.

      WGCNV median scores of 5 histological subtypes of LNMIA with three tiered architectural grades are shown in Table1. The WGCNV scores have a positive correlation with either histological subtypes and architectural grading system (Figure1 A and B). The differences of WGCNV scores are detected betweem two predominant subtypes in one cancerous nodule.

      GWCNV scores display a positive correlation with three tiered architectural grading system and may has a potential value to predict prognosis in LNMIA.

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      JCSE01.17 - Weekly Nab-Paclitaxel Plus Carboplatin as Neoadjuvant Therapy for IIIA-N2 Lung Squamous Cell Carcinoma: A Prospective Phase II Study (ID 14706)

      11:15 - 11:15  |  Presenting Author(s): Changli Wang  |  Author(s): Yu Zhang, Jian Quan Zhu, Dongsheng Yue, Xiaoliang Zhao, qiang Zhang, Hui Chen

      • Abstract
      • Slides

      Background
      To evaluate the safety and antitumor activity of weekly nab-paclitaxel combined with carboplatin in patients with advanced stage IIIA-N2 NSCLC patients with squamous histologyFrom April 2015 to August 2017, 36 treatment-naive, pathologically diagnosed IIIA-N2 lung squamous cell carcinoma patients were enrolled and given two cycles of weekly nab-paclitaxel (100mg/m2, day1,8,15 of a 21-day cycle) plus Carboplatin (AUC = 5 at day 1, q3w) as neoadjuvant therapy. Then resectability was assessed and surgery was performed for resectable lesions. Post-operative adjuvant chemotherapy regimens is the combination of Nab-paclitaxel (100mg/m2, qw x 6) and carboplatin (AUC 5, Q3W x 2) for patients with PD, adjuvant chemotherapy regimen will be changed. The primary objective is the safety and efficacy, and the secondary objectives are quality of life and the role of prognostic biomarker SPARC.

      Of 36 patients, 3 stopped treatment due to patient decision. 33 were finally evaluated and 1 is still on treatment. Significant tumor volume shrinkage was seen in some patients after the neoadjuvant therapy. 66.7% patients achieved partial response (PR), 21.2% patients achieved stable disease (SD). Disease control (PR +SD) rate was 87.9%. Finally, 23 patients underwent surgical resection, the respectability rate was 69.7%. 12.1% occurred disease progress and failed to achieve resection, including 3 with local progress and 1 with pulmonary metastatic nodule; Among 22 PR pts, 4 failed to achieve resection, in which 1 was due to heart function, the other 3 due to personal unwillingness. 2 of 7 with stable disease failed to achieve resection; the pathological improvement in T stage and N stage before and after treatment was 81.8% (18/22) and 50% (11/22) respectively. The major adverse event was neutropenia (grade I and II) and no serious AE was found.

      Nab-paclitaxel in combination with Carboplatin showed promising ORR rate and resection rate in of IIIA-N2 lung squamous cell carcinoma. The regimen could be a new chemo option as the neoadjuvant treatment. PFS and OS data will be reported after follow up completing.

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      JCSE01.18 - A Multicenter Survey of One Year Survival Among Chinese Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer (CTONG1506) (ID 14707)

      11:15 - 11:15  |  Presenting Author(s): Qing Zhou  |  Author(s): Ping Yu, Yong Song, Xin Zhang, Gongyan Chen, Yi Ping Zhang, Jianhua Chen, Zhuang Yu, Yi Hu, Xia Song, Diansheng Zhong, Guosheng Feng, Lulu Yang, Lujing Zhan, Luan Di Yao, Yun Chen, Yue Gao, Yi-Long Wu

      • Abstract
      • Slides

      Background
      Previous results of CTONG1506 study showed that gene aberration test rate was increasing in Chinese NSCLC patients and first-line treatment was standardized accordingly. This survey further described one year survival of patients with different gene aberration status and under different first-line treatments.

      CTONG1506 was a two-year series cross-sectional study. Patients with advanced nonsquamous NSCLC who were admitted from August 2015 to March 2016 and who received first-line anti-cancer treatment at one of 12 tertiary hospitals across China were included. Data extracted from medical charts were entered into medical record abstraction forms, which were collated for analysis. Survival information was collected one year after patients were admitted to hospital. One year survival rate and its 95% confidence interval were analysed by Kaplan-Meier method.

      A total of 707 patients were analysed, with mean age of 57 years and 56.7% were male. Among the 487 patients who had survival data, 192 were EGFR- mutation positive (86 mutated in exon 19 [one year survival rate 0.90, 95% CI: 0.81-0.94] and 88 mutated in exon 21 [one year survival rate 0.84, 95% CI: 0.75-0.90]), 27 patients were ALK positive and 164 patients were EGFR and ALK wild type. Most EGFRmutation positive patients (128/192) received tyrosine kinase inhibitors (TKIs) as first-line treatment and most EGFR wild type patients (155/175) received first-line chemotherapy (Chemo). Pemetrexed was the most common non-platinum chemotherapy-backbone agent (120/155) in platinum doublet regimens. One year survival rates are shown in the table.

      abstract 12337 ctogn1506 one-year survival.png

      This national-wide real world study of tertiary hospitals in China revealed that a majority of (>75%) advanced nonsquamous NSCLC patients survived more than one year and was comparable to well-controlled clinical trial results, indicating survival benefits by gene aberration status guided standard of care. This result may be further validated by our on-going two-year survey.

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      JCSE01.19 - ALTER-0303 Study: Tumor Mutation Index (TMI) For Clinical Response to Anlotinib in Advanced NSCLC Patients at 3rd Line (ID 14708)

      11:15 - 11:15  |  Presenting Author(s): Baohui Han  |  Author(s): Jun Lu, Wei Zhang, Bo Yan, Lele Zhang, Jie Qian, Bo Zhang, Shuyuan Wang

      • Abstract
      • Slides

      Background

      Anlotinib is an effective multi-targeted receptor tyrosin kinase inhibitor (TKI) for refractory advanced Non-Small Cell Lung Cancer (NSCLC) therapy at 3rd line. ALTER-0303 clinical trial has been revealed that Anlotinib significantly prolongs progression free survival (PFS; Anlotinib: 5.37 months vs Placebo: 1.40 months) and overall survival (OS; Anlotinib: 9.63 months vs Placebo: 6.30 months) with the objective response rate (ORR) of 9.18% and the disease control rate (DCR) of 80.95%. Here, we sought to understand the gene mutation determinants for clinical response to Anlotinib via next generation sequencing (NGS) upon cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) at baseline.

      Totally 437 advanced NSCLC patients enrolled in ALTER-0303 study, and 294 patients received Anlotinib therapy. Of the 294 patients, 80 patients were analyzed in the present study. Capture-based targeted ultradeep sequencing was performed to obtain germline and somatic mutations in cfDNA and ctDNA. Response analyses upon discovery cohort (n = 62) and validation cohort (n = 80) were performed by use of germline and somatic (G+S) mutation burden, somatic mutation burden, nonsynonymous mutation burden, and unfavorable mutation score (UMS), respectively. Based on the above independent biomarkers and their subtype factors, tumor mutation index (TMI) was developed, and then used for response analysis.

      Our data indicated that the patients harbouring less mutations are better response to Anlotinib therapy (G+S muatation burden, cutoff = 4000, Median PFS: 210 days vs 127 days, p = 0.0056; somatic mutation burden, cutoff = 800, Median PFS: 210 days vs 130 days; p = 0.0052; nonsynonymous mutation burden, cutoff = 50, Median PFS: 209 days vs 130 days; p = 0.0155; UMS, cutoff = 1, Median PFS: 210 days vs 131 days; p = 0.0016). TMI is an effective biomarker for Anlotinib responsive stratification (Median PFS: 210 days vs 126 days; p= 0.0008; AUC = 0.76, 95% CI: 0.62 to 0.89) upon discovery cohort and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0006). Lastly, integrative analysis of TMI and IDH1 mutation suggested a more promising result for Anlotinib responsive stratification upon validation cohort (Median PFS: 244 days vs 87 days; p < 0.0001; AUC = 0.90, 95% CI: 0.82 to 0.97).This study provide a biomarker of TMI to stratify Anlotinib underlying responders, that may improve clinical outcome for Anlotinib therapy on refractory advanced NSCLC patients at 3rd line. Clinical trial information: NCT02388919.

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      JCSE01.20 - Outcome in Small Cell Lung Cancer Patients with Cerebral Recurrence After Prior Prophylactic Cranial Irradiation  (ID 14710)

      11:15 - 11:15  |  Presenting Author(s): Lei Zhao  |  Author(s): Jindong Guo, Xuwei Cai, Xiaolong Fu

      • Abstract
      • Slides

      Background
      Prophylactic cranial irradiation (PCI) is a standard therapy for both limited small cell lung cancer (SCLC) and extensive SCLC patients with good responses to first-line treatment. The aim of this study was to examine outcomes in SCLC patients in a single institution who underwent cerebral recurrence after prior PCI.

      We retrospectively examined the medical records of 219 consecutive SCLC patients who had initially received PCI(25 Gray in 10 fractions) between June 2007 to June 2017. Data were analyzed with regard to age, sex, smoking status, treatment, disease stage, data of PCI, time to cerebral recurrence, site of cerebral recurrence, re-irradiation after cerebral recurrence and time to death. Survival was estimated by the Kaplan-Meier method. Multivariate analyses were performed by the log-rank and Cox’s proportional hazard model test.

      Of the 219 patients undergoing PCI, 180(82.2%) were LD-SCLC and 39(17.8%) were ED-SCLC. The median age was 59 years and the median follow-up time was 23.7 months. The median overall survival (OS) of all patients from the time of diagnosis was 39.0 months (95%CI, 29.6–48.4), in LD-SCLC it was 47.0 months (95%CI, 35.4–58.6), and in ED-SCLC it was 19.0 months (95%CI, 17.0–21.0). The difference was statistically significant with P=0.000.

      Forty-six patients (21.0%) were diagnosed with cerebral recurrence. 30(65.2%) of these presented with oligometastatic disease and 16(34.8%) had non-oligometastatic disease. Cox multivariate analysis identified disease stage (P=0.043) was the only significantly favorable prognostic factor for cerebral recurrence. The median survival time from PCI was 21.0 months (95%CI, 12.5–29.5), in oligmetastatic disease it was 35.0 months (95%CI, 19.0–51.0), and in non-oligometastatic disease it was 16.0 months (95%CI, 12.1–19.9). The difference was statistically significant with P=0.007. Meanwhile, the median time from PCI to cerebral recurrence was 11.0 months (95%CI, 9.5–12.5), in oligmetastatic disease it was 11.0 months (95%CI, 6.7–15.3), and in non-oligometastatic disease it was 10.0 months (95%CI, 8.4–11.6). There was no statistical significance between the two.

      Among forty-six patients with cerebral recurrence, 34 patients underwent re-irradiation using either Re-WBRT (11patients, 23.9%) or SRS /SRT (23patients, 50.0%), another 12 patients (26.1%) did not accept radiotherapy to brain. The median survival time from cerebral recurrence was 10 months (95%CI, 4.1-16.0) for re-irradiation and 4 months (95%CI, 2.3-5.8) for no radiotherapy group, respectively. The difference was statistically significant with P=0.000.

      PCI remains standard therapy for SCLC patients with good responses to first-line treatment. Cerebral recurrence is inevitable, however, cerebral re-irradiation after recurrence is proven to be beneficial for survival.


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      JCSE01.21 - Different Responses to Osimertinib in Primary and Acquired EGFR T790M-Mutant NSCLC Patients (ID 14711)

      11:15 - 11:15  |  Presenting Author(s): Shuyuan Wang  |  Author(s): Bo Zhang, Baohui Han

      • Abstract
      • Slides

      Background
      Primary EGFR T790M could be occasionally identified by routine molecular testing in tyrosine kinase inhibitor TKI-naive non-small cell lung cancer (NSCLC) patients. This study was aimed to compare clinical characteristics of primary and acquired T790M mutations and their responses to Osimertinib in NSCLC patients.
      We collected clinical characteristics of patients diagnosed with epidermal growth factor receptor (EGFR) mutation from 2012 to 2017 in Shanghai Chest Hospital. For patients with primary and acquired T790M mutations, the responses to Osimertinib were analyzed.Primary T790M was identified in 1.03% (61/5900) of TKI-naive patients. Acquired T790M was detected in 45.50% (96/211) of TKI-treated patients. T790M always coexisted with sensitizing EGFR mutations. Primary T790M was always coexisted with 21L858R (45/61) whereas acquired T790M was coexisted with 19del (61/96). Among them, 18 patients with primary T790M mutation acquired Osimertinib and 75 patients with acquired T790M mutation received Osimertinib. The median progression-free survival (mPFS) of Osimertinib in primary T790M group was greatly longer than that in acquired T790M group (18.0 months:95% CI:15.0-21.0 VS 10.0months:95% CI:8.3-11.7, P=0.016). The DCR of both groups were 89.3% and 100%. In primary T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 15.7m and 24.0 m, respectively. In acquired T790M group, the mPFS of concomitant occurrence of 20 T790M and 21 L858R or 19del were 11.0m and 10.0m, respectively.

      Primary and acquired T790M-mutation patients showed different molecular characteristics. Both of them may respond to Osimertinib. However, primary T790M patients showed greater survival benefits from Osimertinib than acquired T790M patients.

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      JCSE01.22 - Differential Molecular Mechanisms Associated with Dramatic and Gradual Progression in NSCLC Patients with Intrathoracic Dissemination (ID 14713)

      11:15 - 11:15  |  Presenting Author(s): Ying Chen  |  Author(s): Bao Hua, Wei Li, Chao Zhang, Wen-Fang Tang, Ao Wang, Xue Wu, Jing-Hua Chen, Jian Su, Yang W. Shao, Yi-Long Wu, Wen-Zhao Zhong

      • Abstract
      • Slides

      Background
      Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development.We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters.We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors.NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTENmutations, as well as chromosome 18q loss are associated with rapid progression.

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      JCSE01.22a - Tislelizumab Combined With Chemotherapy as First-Line Treatment in Chinese Patients With Advanced Lung Cancer (ID 14702)

      11:15 - 11:15  |  Presenting Author(s): Jie Wang  |  Author(s): Jun Zhao, Zhijie Wang, Zhiyong Ma, Jiuwei Cui, Yongqian Shu, Zhe Liu, Ying Cheng, Shiang Jiin Leaw, Jian Li, Fan Xia

      • Abstract

      Background
      Immune checkpoint inhibitors have shown efficacy in patients with NSCLC as monotherapy and in combination with chemotherapy. Tislelizumab is a humanized IgG4 monoclonal antibody to PD‑1 specifically engineered to minimize FcϒR binding on macrophages, possibly minimizing negative interactions with other immune cells. In a phase 1 study, tislelizumab was generally well tolerated and showed antitumor activity; 200mg IV Q3W was established as the recommended dose.

      This multi-arm phase 2 study, consisting of safety run-in and dose-extension phases, assessed tislelizumab in combination with platinum-based chemotherapy (by tumor histology) as a potential first-line treatment for Chinese patients with lung cancer. All patients received tislelizumab at 200mg Q3W in combination with 4–6 cycles of platinum-doublet until disease progression. Nonsquamous (nsq) NSCLC patients received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, while squamous (sq) NSCLC patients received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and small-cell lung cancer (SCLC) patients received etoposide + platinum Q3W. Tumor response (RECIST v1.1) and safety/tolerability were evaluated.

      As of 21 Feb 2018, 48 patients (median age, 62 years [range: 36–75], 71% male, 71% current/former smokers) received tislelizumab treatment (median, 3 cycles [range: 1–7]); 44 patients remain on the study. Across the four cohorts, confirmed and unconfirmed partial responses were observed in 13 and 9 patients, respectively (Table). The most frequent AEs were chemotherapy-related hematologic toxicities. The most commonly reported grade ≥3 treatment-related AEs were neutropenia (20.8%) and anemia (12.5%); the most common grade 3 immune-related AEs were pyrexia (6.3%) and rash (6.3%). One sq‑NSCLC patient experienced a fatal myocarditis/myositis following one cycle of paclitaxel/cisplatin; all other treatment-related AEs were managed/resolved by study-drug interruption (n=15) or discontinuation (n=4) and appropriate treatment.

      Best Overall Response (Patients With ≥1 Post-Baseline Tumor Assessment)

      nsq-NSCLC (n=9)

      sq-NSCLC [A] (n=12 )

      sq-NSCLC [B] (n=5 )

      SCLC (n=8)

      Total

      (N=34)

      PR

      4 (44.4)

      9 (75)

      4 (80)

      5 (62.5)

      22 (64.7)

      Confirmed PR

      1 (11.1)

      4 (33.3)

      4 (80)

      4 (50)

      13 (38.2)

      Unconfirmed PR

      3 (33.3)

      5 (41.7)

      0 (0)

      1 (12.5)

      9 (26.5)

      SD

      3 (33.3)

      2 (16.7)

      1 (20)

      2 (25)

      8 (23.5)

      PD

      1 (11.1)

      0 (0)

      0 (0)

      1 (12.5)

      2 (5.9)

      NE

      1 (11.1)

      1 (8.3)

      0 (0)

      0 (0)

      2 (5.9)

      Data presented as n (%).

      Abbreviations: nsq-NSCLC, non-squamous non-small cell lung cancer; NE, not evaluable; PD, progressive disease; PR, partial response; SCLC, small cell lung cancer; SD, stable disease; sq-NSCLC, squamous non-small cell lung cancer.

      Tislelizumab, in combination with platinum doublets, demonstrated preliminary antitumor activity and was generally well tolerated in patients with advanced lung cancer.



Author of

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    ISS13 - Symposium Supported by Medscape: Progress of the NSCLC Revolution: Questioning the Experts (Not IASLC CME Accredited) (ID 864)

    • Event: WCLC 2018
    • Type: Industry Supported Symposia
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 07:00 - 08:00, Room 107
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      How Are We Doing in the Delivery of the NSCLC Revolution? (ID 14807)

      07:45 - 07:57  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided

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      Welcome and Introductions (ID 12167)

      07:00 - 07:05  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided

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    MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
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      MA26.11 - Effects of Dose Modifications on the Safety and Efficacy of Dacomitinib for EGFR Mutation-Positive NSCLC (ID 13318)

      14:40 - 14:45  |  Author(s): Tony S. Mok

      • Abstract

      Background

      In patients with EGFR mutation-positive advanced stage NSCLC, first-line dacomitinib significantly improved PFS, OS, DoR and time to treatment failure vs gefitinib (ARCHER 1050; NCT01774721).1,2 Dacomitinib starting dose was 45 mg QD for all patients, with reductions to 30 or 15 mg QD permitted. We explored effects of dacomitinib dose reduction on safety and efficacy in this ongoing study.

      Method

      Patients with newly diagnosed stage IIIB/IV or recurrent NSCLC harboring an EGFR mutation (exon 19 del or exon 21 L858R) randomized to dacomitinib received 45 mg PO QD. Study endpoints and protocol-defined dose reduction parameters were previously described.1 We evaluated reasons for dose reductions, and their effects on incidence and severity of common adverse events (AEs) and key efficacy endpoints (PFS, OS, ORR). Data cutoff dates: 17-Feb-2017 (OS), 29-Jul-2016 (other endpoints).

      Result

      Overall, 150 (66.1%) patients dose reduced for AEs (87 and 63 reduced to 30 and 15 mg QD as lowest dose, respectively); most commonly for skin toxicities (62.6%) and diarrhea (14.0%). Median time to each successive dose reduction was ~12 weeks. Incidence and severity of AEs declined following dose reduction, including grade ≥3 diarrhea (11.3% before vs 4.0% after), dermatitis acneiform (15.3% vs 6.7%), stomatitis (3.3% vs 2.7%) and paronychia (7.3% vs 4.7%).

      PFS was similar in dose-reduced and all dacomitinib-treated patients (Figure).

      pfzusdt200581 dacomitinib dose reduction figure 02.jpg

      Median OS results were also similar (dose-reduced patients: 36.7 mo [95% CI: 32.6, NR]; all dacomitinib-treated patients: 34.1 mo [95% CI: 29.5, 37.7] as were ORRs (dose-reduced patients: 79.3% [95% CI: 72.0, 85.5]; all dacomitinib-treated patients: 74.9% [95% CI: 68.7, 80.4]).

      Conclusion

      Efficacy was similar in the dose-reduced patients and the overall study population. Incidence/severity of dacomitinib-related AEs decreased with dose reduction, thereby allowing patients to continue treatment.

      References:

      Wu, et al. Lancet Oncol. 2017.

      Mok, et al. J Clin Oncol. 2018.

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    OA07 - Oligometastasis: What Should Be the State-Of-The-Art? (ID 905)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
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      OA07.02 - ATOM: A Phase II Study to Assess Efficacy of Preemptive Local Ablative Therapy to Residual Oligometastases After EGFR TKI (ID 12977)

      15:25 - 15:35  |  Author(s): Tony S. Mok

      • Abstract

      Background

      NSCLC patients (Pts) harboring EGFR mutation invariably develop resistance to EGFR TKI at a median time of 9-13 months. Prior studies have showed that local ablative therapy (LAT) upon oligoprogression (OP) can extend the duration of TKI therapy effectively. We postulate that residual positron emission tomography (PET) avid lesions after initial treatment of EGFR TKI may harbor resistant clones and preemptive LAT may improve progression free survival (PFS).

      Method

      This single-arm phase II study aims to determine the efficacy of preemptive LAT to residual metabolic active oligo-metastases after initial TKI. Pts with stage IIIB/ IV EGFR M+ NSCLC who possessed oligoresidual (OR) disease (≤ 4 PET-avid lesions with SUV ≥2.5) after a 3-mth TKI therapy were enrolled. Those with initial PR underwent screening PET-CT. PET avid ORs would be treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians’ discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was done on the 3rd and 12th month post-LAT (or at progression), apart from regular imaging. Further LAT was allowed if OP was detected. Primary endpoint was PFS rate at 1 year from enrollment. Overall survival (OS), treatment safety and comparison with screen failure cohorts were secondary endpoints.

      Result

      18 Pts were enrolled from 2014-17. Recruitment was stopped before the planned number (n = 34) due to slow accrual. Two were not analyzed due to consent withdrawal and significant protocol violation. Median follow up was 28.7 mth. Among the 16 analyzed Pts, the 1 year PFS rate (i.e. 15 mth post TKI) was 62.5%. OS data was not yet mature. All LAT were done by SABR, and none experienced ≥grade 3 SABR related toxicities. Compared with screen failure cohort (n = 43, metabolic CR or PR with residual disease not fulfilling LAT criteria), the 1 year and 2 year PFS favored treatment arm, though statistically not significant (62.5% vs 47.1%, 30.0% vs 7.9%; p = 0.15).

      Conclusion

      The 1-yr PFS rate is encouraging. A trend of improved long term PFS is noted in Pts receiving preemptive LAT to residual PET-avid OM after initial TKI compared with Pts without LAT. Further studies are warranted.

      Clinical Trial information: NCT01941654

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    OA12 - Novel Therapies in MET, RET and BRAF (ID 921)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
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      OA12.07 - Clinical Activity of LOXO-292, a Highly Selective RET Inhibitor, in Patients with RET Fusion+ Non-Small Cell Lung Cancer (ID 13922)

      16:20 - 16:30  |  Author(s): Tony S. Mok

      • Abstract

      Background

      RET kinase gene fusions are actionable drivers that occur in ~2% of non-small cell lung cancers (NSCLC). However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET fusion+ NSCLC patients has been limited. LOXO-292 is a highly selective RET inhibitor, with preclinical activity against diverse RET fusions, potential acquired resistance mutations, and against brain metastases.

      Method

      LIBRETTO-001 is a multicenter global phase 1/2 study (26 sites, 9 countries) enrolling patients w/ advanced solid tumors (NCT03157128) including RET fusion+ NSCLC. Patients are dosed orally in 28-day cycles with dose escalation following a 3+3 design. The primary endpoint is MTD/recommended dose determination. Secondary endpoints include safety, overall response rate (ORR, RECIST 1.1) and duration of response (DoR). Initial data were presented at the ASCO 2018 Annual Meeting.

      Result

      As of 02-April 18, 82 solid tumor patients (including 38 RET fusion+ NSCLC) were treated at 8 doses (20 mg QD-240 mg BID). The MTD was not reached. AEs (≥10% of patients) were fatigue (20%), diarrhea (16%), constipation (15%), dry mouth (12%), nausea (12%), and dyspnea (11%); most were grade 1-2. 2 TEAEs ≥ grade 3 were attributed to LOXO-292 (Gr3 tumor lysis syndrome, Gr3 increased ALT). Of the 38 RET fusion+ NSCLC pts, 30 had at least 1 post-baseline assessment or discontinued LOXO-292 prior to such assessment. 26 of 30 patients (87%) had >20% radiographic tumor reduction (range: -21 to -72%). The ORR was 77% (23/30, 3 responses pending confirmation) with a confirmed ORR of 74% (20/27, excluding 3 patients with unconfirmed responses). The response rate was similar regardless of prior MKI treatment (12/15 MKI-naïve, 11/15 MKI pretreated). Responses occurred independent of upstream fusion partner when known (13/16 KIF5B vs 9/11 other) and included patients w/ baseline brain metastases. Most patients remained on treatment (33/38), including all responders. The median DoR was not reached (longest response was the first responder: >10+ months). Rapid plasma clearance of RET variants was observed, with complete clearance by day 15 in 10 of 17 (59%) NSCLC patients with assessable baseline and day 15 ctDNA.

      Conclusion

      LOXO-292 was well-tolerated and had marked antitumor activity in RET-fusion+ NSCLC patients, including those w/ resistance to prior MKIs and brain metastases. Phase 2 cohorts are now open globally (160 mg BID). Updated safety and efficacy data as of 19 Jul 2018 will be presented.

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-02 -  eXalt3: Phase 3 Randomized Study Comparing Ensartinib to Crizotinib in Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients (ID 13294)

      16:45 - 18:00  |  Author(s): Tony S. Mok

      • Abstract

      Background

      Ensartinib (X-396) is a novel, potent ALK small molecule tyrosine kinase inhibitor (TKI). It is well-tolerated and has shown promising activity in NSCLC patients in a phase 1/2 study in patients that were both ALK TKI naïve and patients that received prior crizotinib, as well as those with CNS metastases. The safety profile of ensartinib appears to be different from other ALK TKIs.

      Method

      In this global, phase 3, open-label, randomized study, approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized with stratification by prior chemotherapy (0/1), performance status (0-1/2), brain metastases at screening (absence/presence), and geographic region (Asia /other), to receive oral ensartinib (225 mg, once daily) or crizotinib (250mg, twice daily) until disease progression or intolerable toxicity.

      Eligibility also includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The primary endpoint is progression-free survival assessed by independent radiology review based on RECIST v. 1.1 criteria. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05.

      Phase 3 recruitment began in June, 2016 and currently has 98 active sites in 21 countries. The duration of recruitment will be approximately 28 months. This study is registered with ClinicalTrials.Gov as NCT02767804.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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    PL01 - Patients First (ID 849)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track:
    • Presentations: 1
    • +

      PL01.03 - Trials that Matter! (ID 11645)

      08:40 - 08:55  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided

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    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 1
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      PL02.07 - IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC (ID 12892)

      09:00 - 09:10  |  Author(s): Tony S. Mok

      • Abstract

      The abstract for this presentation is currently under embargo and will be made available on the day this presentation takes place.

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    YI01 - Young Investigators Session (ID 988)

    • Event: WCLC 2018
    • Type: Young Investigator Session
    • Track:
    • Presentations: 1
    • +

      YI01.13 - How to give a Great Presentation (ID 14682)

      10:30 - 10:45  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided