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Amir Onn



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    MA 02 - Emerging Targets (ID 656)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      MA 02.06 - BRAF Mutant NSCLC: Correlation with PD-L1 Expression,TMB, MSI and Response to ICPi and Anti-BRAF Therapy (ID 10473)

      11:00 - 12:30  |  Author(s): Amir Onn

      • Abstract
      • Presentation
      • Slides

      Background:
      The efficacy of immune check-point inhibitors (ICPi) in BRAF mutant non-small cell lung cancer (NSCLC) is largely unknown. The correlation with different parameters predicting efficacy of ICPi (e.g., PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability status (MSI) in these tumors needs further evaluation.

      Method:
      A retrospective analysis of 30 patients with BRAF mutant advanced NSCLC treated between Aug 2013 and May 2017 was performed. The patients were divided into 2 groups: BRAF V600 E (Group A, N=16), non-V600E BRAF (Group B, N=14). PD-L1 was assessed by immunohistochemistry using 22C3 Dako antibody clone on Dako or Ventana's platform in 16 patients. TMB and MSI were assessed in 9 and 11 patients, respectively. Median progression-free survival (mPFS) with ICPi and targeted agents as well as median overall survival (mOS) were assessed in each group by Kaplan-Meier method.

      Result:
      Baseline characteristics of the cohort: median age 66y (range 39-98); males 53%; current/past smokers/never smokers/NA 13%/44%/40%/3%; adenocarcinoma/other histology 80%/20%; ECOG PS 0/1/2/3/4/NA 27%/33%/10%/13%/0%/17%. The distribution of TMB, PD-L1 expression and MSI status between the 2 groups is presented in Table 1. Ten patients received ICPi (nivolumab-8, pembrolizumab-2), and thirteen patients received anti-BRAF therapy (dabrafenib+trametinib-6, dabrafenib-4, vemurafenib-3). mOS and mPFS with ICPi and anti-BRAF therapy are summarized in Table 1. Four patients with BRAF V600 E PD-L1 ≥ 50% tumors were included in the series; one patients responded to dabrafenib+trametinib combination (response ongoing, 7.1months+); in two patients ICPi were initiated, response assessment pending. One patient with a non-V600E BRAF mutant NSCLC responded to dabrafenib for 6.7 months.Figure 1



      Conclusion:
      BRAF mutant NSCLC tumors are associated with high level of PD-L1 expression, low/intermediate TMB and MSI stable status. ICPi may induce prolonged responses both in BRAF V600E and non-V600E BRAF mutant NSCLC. Some non-V600E BRAF mutant NSCLC may benefit from anti-BRAF targeted therapy.

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    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P3.03-028 - WINTHER – a Study of Cancer Therapy Based on Tumor and Normal-Matched Biopsies – the Sheba Medical Center Lung Cancer Experience (ID 10383)

      09:30 - 16:00  |  Presenting Author(s): Amir Onn

      • Abstract

      Background:
      Patient-tailored therapy based on tumor genomics is limited to 30-40% of the patients whose tumor harbor actionable DNA mutations or amplifications.

      Method:
      WINTHER is an international open label non-randomized clinical trial developed by the WIN consortium. Matched tumor and normal tissue biopsies are collected and analyzed by NGS (Foundation Medicine) or by functional genomics utilizing a prediction model of efficacy developed at Ben Gurion University.

      Result:
      56 patients were biopsied. 29 (52%) had lung cancer. Successful biopsies yielding sufficient material for full genomic analyses were achieved in 29 subjects (53%). Lung biopsy success rates were 71% and 61% respectively for normal and tumor specimens. To date, 11 lung cancer patients were treated with chemotherapy (1) or biologic agents (11). Targeted genomic alterations included EGFR (3), RET (2), KRAS (2), ALK (1), ErbB2 (1), ErbB3 (1), BRAF (1). Clinical benefit rate (CBR) was 55% (6/11) with 1 subject achieving compete response, 2 partial response and 3 stable disease. Response durations were 7, 14 and 18 months.

      Conclusion:
      Tumor genomic analysis based on the comparison of matched tumor and normal biopsies is acceptable and feasible. The experience of the multidisciplinary team is an important contributor to the program’s success.