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I. Monnet



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    MA16 - Novel Strategies in Targeted Therapy (ID 407)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      MA16.03 - Global RET Registry (GLORY): Activity of RET-Directed Targeted Therapies in RET-Rearranged Lung Cancers (ID 4325)

      14:20 - 15:50  |  Author(s): I. Monnet

      • Abstract
      • Presentation
      • Slides

      Background:
      GLORY is a global registry of patients with RET-rearranged non-small cell lung cancer (NSCLC). In order to complement ongoing prospective studies, the registry’s goal is to provide data on the efficacy of RET-directed targeted therapies administered outside the context of a clinical trial. We previously reported results from our first interim analysis (Gautschi, ASCO 2016). Following additional accrual into the registry, updated results are presented here, with a focus on an expanded efficacy analysis of various RET inhibitors.

      Methods:
      A global, multicenter network of thoracic oncologists identified patients with pathologically-confirmed NSCLC harboring a RET rearrangement. Molecular profiling was performed locally via RT-PCR, FISH, or next-generation sequencing. Anonymized data including clinical, pathologic, and molecular features were collected centrally and analyzed by an independent statistician. Response to RET tyrosine kinase inhibition (TKI) administered off-protocol was determined by RECIST1.1 (data cutoff date: April 15, 2016). In the subgroup of patients who received RET TKI therapy, the objectives were to determine overall response rate (ORR, primary objective), progression-free survival (PFS), and overall survival (OS).

      Results:
      165 patients with RET-rearranged NSCLC from 29 centers in Europe, Asia, and the USA were accrued. The median age was 61 years (range 28-89 years). The majority of patients were female (52%), never smokers (63%), with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent metastasic sites were lymph nodes (82%), bone (51%) and lung (32%). KIF5B-RET was the most commonly identified fusion (70%). 53 patients received at least one RET-TKI outside of a clinical protocol, including cabozantinib (21), vandetanib (11), sunitinib (10), sorafenib (2), alectinib (2), lenvatinib (2), nintedanib (2), ponatinib (2) and regorafenib (1). In patients who were evaluable for response (n=50), the ORR was 37% for cabozantinib, 18% for vandetanib, and 22% for sunitinib. Median PFS was 3.6, 2.9, and 2.2 months and median OS was 4.9, 10.2, and 6.8 months for cabozantinib, vandetanib, and sunitinib, respectively. Responses were also observed with nintedanib and lenvatinib. Among patients who received more than one TKI (n=10), 3 partial responses were achieved after prior treatment with a different TKI.

      Conclusion:
      RET inhibitors are active in individual patients with RET-rearranged NSCLC, however, novel therapeutic approaches are warranted with the hope of improving current clinical outcomes. GLORY remains the largest dataset of patients with RET-rearranged NSCLC, and continues to accrue patients.

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    OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab  (ID 6769)

      11:00 - 12:30  |  Author(s): I. Monnet

      • Abstract
      • Presentation
      • Slides

      Background:
      Checkpoint inhibitors such as the anti–PD-1 monoclonal antibody pembrolizumab have demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Although checkpoint inhibitors are rapidly becoming a standard-of-care therapy in multiple tumor types, the optimal treatment duration has not been established. We assessed outcomes in patients who completed the maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study (NCT01905657), in which pembrolizumab provided superior OS over docetaxel in patients with previously treated, PD-L1–expressing advanced NSCLC.

      Methods:
      1034 patients with advanced NSCLC that progressed after ≥2 cycles of platinum-based chemotherapy (and an appropriate therapy for targetable EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to docetaxel 75 mg/m[2] until disease progression, intolerable toxicity, or physician or patient decision; the maximum duration of pembrolizumab was 24 months of uninterrupted treatment or 35 cycles, whichever was later. Response was assessed per RECIST v1.1 by independent central review every 9 weeks. After completion of 24 months/35 cycles, patients continued to undergo imaging every 9 weeks; patients with subsequent disease progression were eligible for a second treatment course if they did not receive other anticancer therapy after stopping pembrolizumab.

      Results:
      In the overall population, median OS was longer (10.5 months for pembrolizumab Q2W, 13.4 months for pembrolizumab Q3W, and 8.6 months for docetaxel) and 24-month OS rates were higher (30.1%, 37.5%, and 14.5%, respectively) with pembrolizumab compared with docetaxel. Of the 691 patients allocated to pembrolizumab, 47 patients received 35 cycles of pembrolizumab and were included in this analysis. As of the September 30, 2016 data cutoff date, all patients had completed all 35 cycles of treatment, but one withdrew from the study treatment after completing 35 cycles. Best overall response (ORR) among these 47 patients was complete response (CR) in 3 (6%) patients and partial response (PR) in 39 (83%) patients, for an ORR of 89%; 5 (11%) patients experienced stable disease (SD). Two of these patients experienced disease progression since stopping pembrolizumab and two of these patients resumed pembrolizumab therapy. As of the cutoff date, none of the 47 patients had died.

      Conclusion:
      With long-term follow-up, the OS benefit has been maintained and pembrolizumab continues to demonstrate superiority over docetaxel. Pembrolizumab provides durable clinical benefit with few patients progressing after completing two years of therapy.

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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-036 - Lung Cancer Screening Program Is Cost Effective in French Setting: A Model Based Study (ID 5054)

      14:30 - 15:45  |  Author(s): I. Monnet

      • Abstract

      Background:
      The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung cancer-mortality. There is no data's on the faisability and cost-effectiveness of CT lung cancer screening program in the French setting.

      Methods:
      We estimated mena life-years gaineds, costs and incremental cost-effectiveness ratio (ICER) for screening with low-dose CT compare to no screening. Estimations of life-years gained were based on the efficacy of NLST trail applied to the general french population using the same inclusion criteria's that NLST trail (age of 55 to 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting) adjusted to sex, age and smoking status. Costs were limited to directs costs from the payers perspective. We also performed sensitivity analysis based on several asssumptions of program efficacy.

      Results:
      The target population was 5 551 141 subjects. Compared with no screening, screening with low-dose CT, over a period of 2 years, will have an additional cost of 941 978 €, will provide 52.4 additional year of life with a corresponding ICER of 17 969 € per year gained. Sensititiviy analysis showed that this result is sensitive to program efficacy (number, stage and survival of lung cancer diagnosed by the program) and to subjects compliance rate to the program.

      Conclusion:
      Cost effectiveness of CT lung cancer screening program in a French population using the same main inclusion criteria and outcomes of NLST trial appears as acceptable from the french health system

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    P3.02a - Poster Session with Presenters Present (ID 470)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02a-004 - NSCLC Patients Harboring ALK Translocation: Clinical Characteristics and Management in Real World Setting. EXPLORE GFPC 02-14 (ID 5043)

      14:30 - 15:45  |  Author(s): I. Monnet

      • Abstract

      Background:
      ALK (Anaplastic Lymphoma Kinase) translocation is a rare oncogenic driver in NSCLC (Non Small Cell Lung Cancer) (3 to 5%) and few data are published on the management of these patients outside patients included in clinical trial. objective:to investigate clinical characteristics and management of these patients in real world setting.

      Methods:
      inclusion of patients with a diagnosis of NSCLC harboring ALK translocations between January 2012 and December 2014, collection of demographic and clinical characteristics, risk factors, Progression free survival (PFS), Overall Survival (OS), mode of progression and therapeutic management

      Results:
      132 patients recruited in 31 centers: 67(51%) men; age: 60.1 ± 14,5 years; PS 0/1 at diagnosis: 89%; non smokers:79%, adenocarcinoma: 93%; Stage at diagnosis 4/3/2-1:74%/19%/7%: co-mutations EGFR n=2, BRAF n=2, KRAS = 1, HER2 = 1. Outcomes of stage IV (n=97): first line treatment: chemotherapy: 75%, Best supportive care (BSC): 1 %, anti ALK: 24 %; response rate, disease control rate (DCR) and PFS to first line treatment: 42 %,64% and 7.5 months (CI 5.9 ;9.5), second line treatment (n=60): chemotherapy: 25%, anti BRAF 72%, BSC 3 %; response rate, DCR and PFS to second line treatment: 43.4%,70% and 4,7 months (CI 4.0; 8.1); 2 years-OS: 56.7% (CI 45.5 ;70.4), mediane OS was not reach.

      Conclusion:
      In this real world analysis, the majority of NSCLC patients with ALK translocation were non smokers,adenocarcinoma and appears to have a better survival to NSCLC pts without oncogenic driver. Clinical trial information: Supported by an academic grant from Lilly, Astra Zeneca, boehringer ingelheim

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-089 - ImmunoCHIC: A Prospective Nivolumab Monotherapy Cohort in Advanced Non-Small Cell Lung Cancer Patients in Routine Clinical Practice  (ID 5839)

      14:30 - 15:45  |  Author(s): I. Monnet

      • Abstract

      Background:
      in France, in May 2015, Nivolumab early access program was established for patients with advanced NSCLC progressing during or after platinum-based chemotherapy. There is little evidence of Nivolumab use out of clinical trials. We report here one year of Nivolumab use in a French Universitary hospital.

      Methods:
      Observational prospective review of patients with advanced NSCLC treated with Nivolumab monotherapy (3 mg/kg/2weeks) in our center, in routine clinical practice. Patients in clinical trial were excluded. Analyze was done on clinico-pathological features, tolerance and outcomes.

      Results:
      63 patients were included (men: 76.1%, age: 65 (range: 40–78), squamous: 33.3%; smoker: 93.7%%, EGFR/ALK negatives: 98.4%, unknown PDL1: 70%; at least one significant comorbidity: 54%; performans status 0/1/2: 34%/49%/17%; cerebral metastasis: 38%; nivolumab as second, third and more than third lines: 38%/38%/24%. Median number of nivolumab cycles: 6 (1-24), more than 12 cycles: 20.6% Disease control rate : 59% (3 complete responses) ; Clinically significant adverse event: 13 (20%) patients (asthenia: 4 patients, grade 2 to 4 colitis: 3 patients, pneumoniae: 3 patients, nephritis: 1 patient). After Nivolumab, 50% of the patients received an another systemic therapy. Two patients were able to go back to work.

      Conclusion:
      In real life setting, nivolumab had the efficacy level reported by pivotal clinical trial but with a higher rate of clinically significant adverse events, particularly colitis.

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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-061 - Burden of Disease and Managment of Mesothelioma in France: A National Cohort Analysis (ID 5072)

      14:30 - 15:45  |  Author(s): I. Monnet

      • Abstract

      Background:
      Malignant pleural mesothelioma (MPM) is an uncommon cancer with poor survival. The aim of this study was to determine the burden of MPM disease in France and analyze associations between socio-economic deprivation, population density, management and outcomes of MPM.

      Methods:
      We used a national hospital data base (PMSI-MCO) to extracted MPM incidents patients of years 2011 and 2012 (ICD-10 codes C45.0 and C54.9 as principal/related or significantly associated diagnosis (PD,RD, SAD) in 2011 and 2012, without MPM codes or C34/C38.4 codes as PD/RD/SAD since 2006). Patients were followed for two years after the initial diagnosis. Cox models were used to analysis one and two-years survival according to sex, age, comorbidities, management, a population density index (PDI) and a social deprivation index (SDI) based on census data aggregated at the municipalities level.

      Results:
      1890 patients were included on the analysis (men: 76%, age: 73.6 ± 10 years, significant comorbidities: 84%). Patients lived in urban zones in 57% cases and in hight deprivated areas in 53%. Only 1% had a curative surgical procedure; 65% received at leat one dose of chemotherapy (72% at least one administration of chemotherapy with pemetrexed, 28% at least one administration with pemetrexed - bevacizumab); 42% and 20% of the patient received chemotherapy on the last three and the last months of their life, respectively); Survival rate at one- and two-year were 64% and 48% respectively. In multi-variate analysis men, older, patients with chronic renale failure, patients with chronic respiratory failure and patients who didn't receive pemetrexed at any time of their management had worse pronostic. Adjusting analysis on age, gender, comorbidities (hypertension, diabetisi, COPD), leaving in rural/semi rural area was associated with a better survival at one and two-year, HR: 0.82 (0.72-0.96) and HR: 0.83 (0.73-0.94); social deprivation index was not a significant variable for survival. The mean cost management per patient was 27 624 ± (15894 ) euros (31.4% of this cost was the cost of pemetrexed and bevacizumab).

      Conclusion:
      MPM remained an uncommon disease, with less of 1000 new cases a year in France, with a very poor pronostic and a significant burden for National Health system.