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E. Wasielewski



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    MA 03 - Chemotherapy (ID 651)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA 03.10 - Prognostic Factors in NSCLC Patients Treated with a Fourth-Line Therapy (ID 7455)

      11:00 - 12:30  |  Author(s): E. Wasielewski

      • Abstract
      • Presentation
      • Slides

      Background:
      Emergence of new active drugs and improvement in supportive care make it more likely for patients with advanced NSCLC to receive a fourth-line therapy.However, no survival benefit of such treatment has ever been demonstrated yet, although some studies suggest that it may be effective in selected patients. A better selection could avoid exposing patients to futile and toxic treatments. We conducted a study aiming at identifying prognostic factors in patients with advanced NSCLC treated with a fourth-line therapy.

      Method:
      In this retrospective, multicentric study, patients with advanced NSCLC receiving a fourth-line therapy were included. Factors associated with prolonged overall survival (OS, defined as OS >6 months) were identified by univariate and multivariate analysis using a Forward method.

      Result:
      151 patients were included in this study between Jan 2015 and Dec 2016. Median age was 60 (range 55-64). Most patients were male (70%) and had adenocarcinoma (72%). Most common prior treatments included platinum-based chemotherapy (92%), single-agent chemotherapy (81%), targeted therapies (46%) and immunotherapy (9%). Median OS was 7.39 months (6.7-9.43). Nine factors were significantly associated with OS >6 months: current smoker (Hazard Ratio (HR) 1.99, 95% confidence interval[1.16-3.41]), former smoker (HR 0.51[0.30-0.98]), Karnofsky Index (KI) ≥ 90% at the start of fourth-line therapy (HR 0.35[0.19-0.65]), weight loss since first-line therapy (HR 1.85[1.06-3.23]), early stage at diagnosis (HR 0.48[0.24-0.96]), number of cycles and delay since first-line therapy (HR 0.94[0,89-0,99]and 0.99[0.99-1]), Progressive Disease (PD) as Best Objective Response (BOR) in the first 3 lines of treatment (HR 2.92[1.9-5.37]), absence of grade ≥ 3 Adverse Events (AEs) during first-line therapy(HR 0.54[0.31-0.94]). Among them, 4 independent variables were found to be statistically significant by multivariate analysis, including early stage at diagnosis (HR 0.37[0.16-0.58]), absence of grade ≥ 3 AEs during first-line therapy (HR 0.56[0.32-0.98]), PD as BOR in the first 3 lines of treatment (HR 3.06[1.64 -5.73]) and KI ≥ 90% at the start of fourth-line therapy (HR 0.31[0.16-0.58]).

      Conclusion:
      We highlighted 4 factors significantly associated with OS >6 months in patients treated with fourth-line advanced NSCLC. These factors need to be prospectively assessed to confirm if they could help identifying patients who may benefit from fourth-line therapy.

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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-002 - Liquid and Solid Rebiopsies in EGFR-Mutated NSCLC Patients (ID 8442)

      09:30 - 16:00  |  Author(s): E. Wasielewski

      • Abstract

      Background:
      Treatment of EGFR-mutated NSCLC patients with acquired resistance to EGFR tyrosine kinase inhibitors (TKI) relies on identification of the mechanism of resistance.

      Method:
      We performed a retrospective multicentric study in order to investigate use and results of liquid (circulating free DNA) and solid rebiopsies in routine practice.

      Result:
      We included 95 EGFR-mutated NSCLC patients with at least one rebiopsy after treatment with EGFR TKI (mostly 1[st] generation TKI). 87 solid rebiopsies and 71 liquid rebiopsies were performed. The number of liquid biopsies increased over time, from 1/y (6,6% of all rebiopsies in 2014) to 53/y (70,6% of all rebiopsies in 2016). The proportion of liquid biopsies increased with the number of rebiopsies per patient, from 35,5% for the first rebiopsy to 83,3% for the third rebiopsy. The rebiopsy identified a mechanism of acquired resistance in 48 patients (50,5%), including 43 patients with a T790M mutation (45,2%), 2 patients (2,1%) with MET amplification, 1 patient (1%) with small cell lung cancer transformation, 1 patient (1%) with a C797S mutation and 1 patient (1%) with a KRAS mutation. The initial EGFR mutation was found in 74 solid rebiopsies (85%) and 43 liquid rebiopsies (60%). The T790M mutation was found in 32 solid rebiopsies (36,8%) and 18 liquid rebiopsies (25,3%). Among 44 patients having both liquid and solid rebiopsies performed at the same time, an EGFR mutation was found by both techniques in 26 cases (59,1%) and the overall concordance was 88,6%. Analysis of cerebrospinal fluid was positive in 10 patients (100%) for the initial EGFR mutation and 1 patient (10%) for the T790M mutation. A T790M mutation was identified in 37,3% of all first rebiopsies. Repeated rebiopsies when the first biopsy was negative identified the T790M mutation in 29,6% of cases.

      Conclusion:
      In our series representative of daily practice, rebiopsies of EGFR-mutated NSCLC patients with acquired resistance to EGFR TKI identified a mechanism of resistance in half of the cases. Repeating rebiopsies increased the chance of detecting a T790M mutation.