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Christos Chouaid



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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA03.09 - Dramatic Responses to Immune Checkpoint Inhibitors in MET Exon 14 Skipping Mutation (METex14mut) Non Small Cell Lung Cancers (Now Available) (ID 1621)

      10:30 - 12:00  |  Author(s): Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Background

      METex14 mutations occur in 2-3% of Non-Small-Cell Lung Cancers (NSCLC), with a higher prevalence in patients aged over 70-years-old, non-smokers.and women. Crizotinib, a MET-inhibitor, allows remarkable, but often short, tumor responses. Immune Checkpoint Inhibitors (ICIs) have become pivotal treatments in NSCLC but seem less efficient in non-smokers and in case of oncogenic addiction. We report durable strong responses in four non-smoker women (A, B, C, D) and two smokers (E, F) treated by ICIs in a second-line setting for NSCLC harboring METex14 mut.

      Method

      We studied the clinical and biological characteristics and the tumor response after ICIs for each patient. The complete DNA sequencing of the tumor was available after the beginning of ICIs (explaining why crizotinib was not proposed in second line). PDL1 expression on tumor cells was evaluated by antibody clone E1L3N (Cell signaling Technology).

      Result

      Table 1 summarizes patient and tumor characteristics, and the evolution during ICIs : Nivolumab for all patients except E (pembrolizumab). There were neither EGFR, BRAF, KRAS mutations, nor ALK or ROS translocations (except minority KRAS mutation for C). No concurrent MET amplification was found.

      tableau.jpeg

      Partial or complete response was rapidly (2 months) obtained in five patients, while pseudo-progression was first observed in D. After a grade 3 diarrhea and diabetic ketoacidosis, ICI was stopped in A but the reintroduction one year later did not cause any toxicity. The tolerance was excellent for the 5 other patients. Response was maintained from 16 to 40 months and treatment is ongoing in four patients. C stopped ICI after 26 months (Complete response on PETscan). B had an isolated bone progression after 7 months of ICI which benefited from a local radiotherapy. After almost 2 years of ICI, a multisite progression occurred and crizotinib was proposed.

      Conclusion

      ICIs should be discussed in the treatment of METex14 mut NSCLC.

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    MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA07.06 - Immunotherapy Re-Challenge After Nivolumab Treatment in Advanced Non-Small Cell Lung Cancer in French Real-World Setting (Now Available) (ID 1281)

      13:30 - 15:00  |  Author(s): Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Background

      Real‐world evidence of nivolumab as treatment for advanced non-small cell lung cancer (aNSCLC) can complement evidence from clinical trials to optimize routine usage and personalization of care. Further, little is known about treatment options and outcomes after discontinuation of nivolumab.

      Method

      Based on the National hospitals database (PMSI), we built a retrospective cohort of all NSCLC patients (ICD code: C34*) starting nivolumab in 2015-2016 and followed them until Dec 2017. Information on patients’ baseline characteristics (demographics, comorbidities, treatment history) was retrieved. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Time to treatment discontinuation (TTD) and overall survival (OS) were estimated with Kaplan-Meier methodology. Re-challenged patients were analyzed according to their first nivolumab treatment duration i.e. <3; 3-6; ≥6 months.

      Result

      We identified 10,452 NSCLC patients initiating nivolumab during the inclusion period (male: 71%; mean age; 63.8±9.6 years; squamous histology: 44%; cerebral metastasis: 17.4%; median aNSCLC history: 12.5 months; previous curative surgery: 15.6%; median time since first chemotherapy: 10.5 months; mean dose of nivolumab: 213±54mg). Median TTD and OS were 2.8 months and 11.6 months. One-year and 2-year OS rates were 48.8% and 27.4%. Overall, 5118 (53.4%) patients received subsequent systemic therapy after nivolumab discontinuation. Among them, 1517 patients (29.6%) were re-treated with anti-PD1 agents (nivolumab: 98.8%) either after a therapeutic break (‘immunotherapy resumption group’: n=1127; mTTD: 4.1 months; mOS: 14.9 months from second initiation) or after chemotherapy (‘immunotherapy re-challenge group’: n=390; mTTD: 3.0 months; mOS: 18.2 months from second initiation). The Figure presents OS curves of the ‘re-challenge group’ according to first nivolumab treatment duration.

      graph os re-challenge according to ttd 1st nivo.jpg

      Conclusion

      After nivolumab discontinuation, around 30% of patients received immunotherapy again, either as a resumption or as a re-challenge following non-immunotherapy treatment. The influence of the first nivolumab treatment duration on re-challenged patients' OS should be further investigated.

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    MA14 - The Adequate MTarget Is Still the Issue (ID 140)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA14.06 - Nintedanib-Docetaxel in 2nd Line Treatment in No Squamous Non-Small Cell Lung Cancer Patients, Refractory to First Line Treatment (GFPC02-15) (Now Available) (ID 558)

      15:45 - 17:15  |  Author(s): Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Background

      Second line chemotherapy used in advanced Non Small Cell Lung Cancer (NSCLC) have demonstrated a slight survival benefit in patient refractory to a first line platinum based doublet chemotherapy. In exploratory analysis, Nintedanib in combination with docetaxel have shown interesting result in second line setting for refractory NSCLC patients.

      Objective: To assess the efficacy in terms of progression-free survival (PFS) of the nintedanib - docetaxel combination in second-line treatment in refractory no squamous NSCLC (NsqNSCL) patients

      Method

      This prospective, multicentric open-label phase II trial, included patients with advanced Nsq NSCLC (EGFR, ALK wild-type), PS 0-1, progressing during the first four cycles of cisplatin-based induction chemotherapy. Patients received Nintedanib (200 mg X2 /d d2-d20)- Docetaxel (75 mg/m2 d1-d21) combination until progressive disease or unacceptable toxicity.

      The primary endpoint was the PFS rate at 12 weeks. Secondary endpoints included median PFS, median overall survival (OS), overall response rate (ORR) and tolerability. Based on a A’Hern’s single-stage phase II design trial (sample size determination is based on exact binomial distribution), the Nintedanib-Docetaxel strategy will be rejected if the primary endpoint was below 22/53 patients at the end of study.

      Result

      The analysis included 53 evaluable patients managed in 21 centers; last patient included at the end of January 2019. Mean age 58.4 years, male 73 %, adenocarcinoma 97.5%, current/former smokers: 42/50 %, PS 0/1: 25%/75%; weight loss >5% : 19%, stage IV: 100% (38% with brain metastasis, median metastasis 2). All patients received for induction chemotherapy, a platin doublet (22% with bevacizumab), number of cycle 1-2/ 3-4: 57%/ 43%.

      Interim analysis reviewed by the independent committee conducted as planned, after the 27 first inclusions concluded that there was no sign of unexpected toxicity (adverse events grade 3-4 :22%, grade 5 :0%) or futility (9 patients meet primary end point on 25 evaluable). The results of the final analysis on the whole population (PFS at 12 weeks (primary end point), median PFS, median OS and toxicity) will be presented at the meeting

      Academic grant from Boehringer Ingelheim

      Conclusion

      Section not applicable

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    OA15 - Targeted Agents and Immunotherapy for Small Cell Lung Cancer (ID 152)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
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      OA15.02 - Carboplatin-Etoposide Versus Topotecan as Second-Line Treatment for Sensitive Relapsed Small-Cell Lung Cancer: Phase 3 Trial (Now Available) (ID 546)

      14:30 - 16:00  |  Author(s): Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Background

      Topotecan is currently the only drug approved in Europe in second line setting for small-cell lung cancer (SCLC). This study investigates whether the doublet carboplatin-Etoposide was superior to topotecan monotherapy as second-line treatment in patients with sensitive relapsed SCLC.

      Method

      this open-label, multicenter, phase 3 trial randomized patients with SCLC that responded to first-line platin etoposide doublet treatment but showed evidence of disease relapse or progression at least 90 days after completion of the first-line treatment. Enrolled patients were randomly assigned (1:1) to receive combination chemotherapy (Six cycles of 3-weeks Carboplatin, AUC 5, day 1 and Etoposide 100 mg/Sqm/d 1-3, intra-venous) or oral Topotecan (2.3 mg/Sqm/d 1-5, every 3 weeks). Primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), quality of life and tolerance in the intention-to-treat population, (clinical trialgouv: NCT02738346)

      Result

      178 patients were screened and 164 randomized in 36 centers, with 82 assigned to each treatment group (age: 64.5 ± 7.2 years, men: 72.8%, PS 0/1/>1: 34.7%/56.3%/ 9%. Median PFS was significantly longer in combination chemotherapy group (4.7 months, 95% CI: 3.9-5.5) compare to topotecan group (2.7 months, 95% CI: 2.3-3.2), HR: 0.6, 95% CI 0.4-0.8, p < 0.002. The ORR were significantly more important in the combination chemotherapy than in topotecan arm (ORR 49 % vs 25 %, p < 0,002), but without difference in term of median OS, 7.5 months (95% CI: 5.4-8.7) in combination chemotherapy group versus 7.4 months (95% CI.6.0-9.3) in topotecan arm. Grade 3/4 neutropenia were significantly more common in the topotecan group than in the combination chemotherapy group (35.8% vs 19.7 %, p < 0.001. There is a non-significant trend for more febrile neutropenia in topotecan arm compare to combination arm (13.6 % 6.2 %, p = 0.19, and no difference for grade 3/4 thrombopenia, 35.8 % vs 30.9 %, and anemia, 24.6 % vs 21 %, for topotecan and combination arms, respectively. Two treatment-related deaths occurred in the topotecan arm (febrile neutropenia with sepsis), none in the combination arm. Results of quality of life outcomes will be presented at the meeting.

      Conclusion

      platin - etoposide re-challenge can be considered as a standard second-line chemotherapy for sensitive relapsed SCLC.

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    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.16-46 - Genetic Testing Patterns, Treatment Characteristics, and Overall Survival in ALK-Positive Metastatic NSCLC Patients Treated with Ceritinib (ID 1345)

      09:45 - 18:00  |  Author(s): Christos Chouaid

      • Abstract
      • Slides

      Background

      In patients with ALK-positive metastatic non-small cell lung cancer (mNSCLC), the majority of data on ALK inhibitor (ALKi) use and related survival outcomes are from clinical trials; information from community practice is sparse. This study therefore sought to assess ALK testing patterns, treatment characteristics, and overall survival (OS) in patients with mNSCLC treated with ceritinib in routine practice.

      Method

      In this retrospective cohort study, medical records for patients with ALK-positive mNSCLC (diagnosed during 2008-2016; aged ≥18 years) were selected from sites in Canada and Europe. Patients were treated with ceritinib in any line for mNSCLC and had at least 8 months of follow-up after ceritinib initiation, except for patients who died sooner than 8 months. Baseline patient characteristics, treatment patterns, and timing of ALK testing relative to start of therapy lines were descriptively assessed. OS was assessed using Kaplan-Meier methods.

      Result

      87 patients were selected (median age: 53 years). Nearly 56% of patients had been tested for ALK mutation before initiating the first-line therapy (1L); 72% were tested before 2L and 77% before 3L. The most common regimens were cisplatin/pemetrexed (25%) in 1L, crizotinib (28%) in 2L, and ceritinib (35%) in 3L. Over two-thirds (68%) received treatment with at least 2 ALKis. The most commonly observed ALKi sequences were crizotinib followed by ceritinib (52%), ceritinib only (23%), and crizotinib followed by ceritinib followed by alectinib (12%). Median OS (95% CI) from mNSCLC diagnosis was 39 (33.1-50.1) months. Median OS (95% CI) from treatment initiation was 36 (28.2-48.9) months for 1L, 29 (22.1-42.8) months for 2L, and 23 (14.0-40.5) months for 3L.

      Conclusion

      Only slightly more than half of patients with ALK-positive mNSCLC were tested for ALK mutation before initiating the first-line therapy during the study period. ALKis were the preferred therapies in the second and third lines. Median OS following the first-line therapy initiation was nearly 3 years among the selected study patients.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-09 - VinMetAtezo: Phase II Trial of Metronomic Oral Vinorelbine with Atezolizumab for Recurrent Stage IV NSCLC (GFPC*04-08) (ID 690)

      10:15 - 18:15  |  Author(s): Christos Chouaid

      • Abstract
      • Slides

      Background

      Immunotherapy is recommended as second-line treatment for advanced Non-Small Cell Lung Cancer (NSCLC) progressing after a platinum doublet treatment. However, response rates remain low and some patients have rapid progression. Novel concepts of synergic action between immunotherapy and chemotherapy have emerged recently. Metronomic oral vinorelbine (MOV) is defined as low-dose and frequent chemotherapy administration. There is no data of the association of immunotherapy and metronomic chemotherapy. The main objective of this trial was to assess safety and efficacy of this combination of MVO and atezolizumab.

      Method

      An open label phase 2 trial (NCT 03801304) in two steps.

      -First step: a safety run-in phase: 12 patients will be enrolled and will receive atezolizumab in combination with MOV (40 mg/day 3 times a week, every week). After 12 patients have received study treatment and completed at least 1 cycle of study treatment (21 days), enrollment will be interrupted and an independent Data Safety Monitoring Board (DSMB) will review the number and percentage of adverse events (AEs). The dose will be considered toxic when Grade ≥ 3 immune-related AEs (>20%) or vinorelbine-related AEs (>20%) occurs. In this case the dose will be decreased to 30 mg, 3 times a week. AEs will be assessed with the same procedure that will be applied to the next 12 patients.

      - Second step: phase II design as defined by A’hern. The main outcome is PFS rate at 4 months. Minimal efficacy hypothesis (p1) is set at 55% event-free rate of PFS at 4 months, (p0), which would indicate that the strategy is clearly ineffective, is set at 40% PFS at 4 months. With a 5% alpha risk (unilateral perspective) and a 20% beta risk, the number of assessable subjects is set at 71.

      Result

      The trial started on 2019 January 24th. 12 patients have been included in 4 centers. The run in step ended at the beginning of April, with no grade 3 or more immune related AEs or vinorelbine related AEs. The DSMB decided to expand the study to the second step, which will start on April, 17th.

      Conclusion

      Combination of atezolizumab and MOV appears as a feasible association without major toxicities. The phase 2 is ongoing; complementary results on safety and efficacy will be presented at the meeting.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-03 - Nivolumab Outcomes in Octogenarian Patients with Advanced Non-Small Cell Lung Cancer in French Real-World Setting (ID 1974)

      10:15 - 18:15  |  Presenting Author(s): Christos Chouaid

      • Abstract

      Background

      Around 10% of patients newly diagnosed non-small cell lung cancer (NSCLC) in France are octogenarian. Knowledge about nivolumab outcomes in such specific population is still limited and real-world data represent a valuable source of information. The aim of this study was to examine use and outcomes of nivolumab in elderly patients aged ≥80 years.

      Method

      Based on the National hospitals database (PMSI), we built a retrospective cohort of all NSCLC patients (ICD code: C34*) initiating nivolumab in 2015-2016 in second- or later-line setting and followed them until Dec 2017. Information on patients’ baseline characteristics (demographics, comorbidities, treatment history) was retrieved for elderly (≥80 years) and non-elderly (<80 years), and time to treatment discontinuation (TTD) with nivolumab and overall survival (OS) were estimated with Kaplan-Meier methodology.

      Result

      Among 10,452 NSCLC patients initiating nivolumab during the inclusion period, 514 (4.9%) were 80 years or over. Mean age at baseline was 82.5 years (±2.4) in elderly and 62.8 years (±8.8) in non-elderly. Compared to non-elderly, patients were more frequently men in elderly group (p<0.001) and had more frequently prevalent hypertension and diabetes (p<0.001). Cerebral metastasis, renal failure, COPD, pulmonary insufficiency and other pulmonary chronic diseases were statistically less frequent in the elderly group (p<0.001). TTD curves showed identical median of treatment duration between both groups (2.8 months). Median OS were found similar between elderly and non-elderly patients (11.5 vs 11.6 months) and, long-term survivals were also comparable with 1-year and 2-year OS rates. Characteristics and outcomes are presented in the table.

      Characteristics and outcomes

      < 80 years

      (N=9938)

      ≥ 80 years

      (N=514)
      p-value
      Demographics
      Gender – Male 7019 (70.6%) 401 (78%) < 0.001
      Mean age (±SD) 62.8 y (±8.8) 82.5 y (±2.4) < 0.001
      Median age (Q1-Q3) 64 y (57-69) 82 y (81-84) < 0.001
      Comorbidities
      Hypertension 1844 (18.6%) 142 (27.6%) < 0.001
      Diabetes 871 (8.8%) 63 (12.3%) < 0.001
      Renal failure 460 (4.6 %) 19 (3.7%) < 0.001
      Chronic obstructive pulmonary disease 1298 (13.1%) 50 (9.7%) < 0.001
      Pulmonary insufficiency 149 (1.5%) 4 (0.8%) < 0.001
      Other chronic pulmonary diseases 870 (8.8%) 33 (6.4%) < 0.001
      Cerebral metastasis 1771 (17.8%) 29 (5.6%) < 0.001
      Lung cancer management care
      Diagnosis to nivolumab initiation - Median (Q1–Q3) 12.4 mo (6.7–24.0) 14.2 mo (7.9–29.9) 0.002
      Nivolumab TTD - Median (Q1–Q3) 2.8 mo (1.4–6.7) 2.8 mo (1.5–6.5) N.S.
      Nivolumab discontinuation 9120 (91.8%) 473 (92.0%) N.S.
      Subsequent systemic treatment 4908 (53.8%) 210 (44.4%) < 0.001
      Overall survival (OS)
      Median OS (Q1 –Q3) 11.6 mo (4.1-26.2) 11.5 mo (5.0-25.2) N.S.
      1-year OS rate 48.8% 47.5% N.S.
      2-year OS rate 27.3% 25.8% N.S.
      N.S.: non significant ; TTD: time to discontinuation
      Conclusion

      A small percentage of patients initiating nivolumab during the study period were aged 80 years or over (<5%). Elderly profile suggests a cautious selection by clinicians, which may also explain similar outcomes than ones in the non-elderly population.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-65 - Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E–Mutant NSCLC in Real World Setting (ID 307)

      10:15 - 18:15  |  Author(s): Christos Chouaid

      • Abstract
      • Slides

      Background

      Dabrafenib plus trametinib (D-T) combination is approved in Europe Union for BRAFV600E–mutant metastatic non-small cell lung cancer(NSCLC) but there is few published data’s on this efficacy and tolerance outside clinical trail results.

      Objective: to assess efficacy and tolerance of D-T in real world setting.

      Method

      Retrospective, multicentric study including BRAF V600E-positive advanced NSCLC receiving D-T outside a clinical trial. Overall survival (OS) and progression free survival (PFS) were analyzed in all population and according lines of D-T treatment (first line treatment or subsequent line treatments).

      Result

      the analysis included 40 BRAF V600E advanced NSCLC patients managed in 14 centers; at diagnosis: mean age 71 ±9.6 years , female 55 %, adenocarcinoma 95 %, currents/formers smokers 17.5%/50 %, At D-T initiation: PS 0-1/2 or+: 86.8%/13.2% , loss weight> 5%: 24%, symptomatic disease: 92%, stage IV: 95% , mean metastatic site: 2.3 (main metastatic sites: pleura: 46%, bone: 33%, respectively).Mean line of treatment before D-T: 1.5. D-T was a first line treatment in 22.5 %, second line or more 77.5% (25% received one BRAF TKI before). Median time between diagnosis and D-T treatment was 0.7 [95%CI: 0.2-1.3] months in first line setting and 17.3 [95%CI: 10.8-27.2] months.

      At the time of analysis 67.5% patients were in treatment with D-T and median follow up since beginning of D-T treatment was 8.7[95%CI: 5-12]months in whole population [7,5, 95%CI: 1-12.3]months for patients treated in first line). D-T dose was modified for 32.5.0% of the patients and definitively discontinued for 12,5 % because of severe adverse events.

      Median PFS and OS were not reach and follow up is continued.

      The mature results of PFS and OS (whole population and subgroups) will be showed to the WLCC meeting.

      Conclusion

      Section not applicable

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