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A. Belilovski Rozenblum



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      145P - Impact of next-generation sequencing on survival in lung cancer (ID 595)

      12:30 - 13:00  |  Author(s): A. Belilovski Rozenblum

      • Abstract
      • Slides

      Background:
      Next-generation sequencing (NGS) enables a comprehensive genomic analysis of lung cancer patients. It has uncovered many novel genetic abnormalities and identified actionable genomic alterations in lung tumors that previously tested “negative” by conventional non-NGS tests. In this study, we evaluated the clinical impact of NGS on overall survival of advanced non-small cell lung cancer (NSCLC) patients.

      Methods:
      In this retrospective study, 234 consecutive stage IIIb/IV NSCLC patients who performed hybrid capturing NGS were enrolled in Israel, between 2011–2017. Hybrid capture-based NGS was performed by Foundation Medicine and Guardant 360[TM] if tissue was not available.

      Results:
      234 consecutive NSCLC patients were included in this study. 62% (145/234) performed tissue NGS and 38% (89/234) performed liquid NGS. Median age at diagnosis was 63 years. 84% had adenocarcinoma. 37% were never-smokers. The patients were divided into 4 groups according to the identification of NCCN-approved actionable genomic alterations on NGS analysis: Group A did not have an actionable target; Group B discovered an actionable target but did not receive targeted treatment, due to high performance status or preference to use immunotherapy for PD-L1 positive patients; Group C received targeted therapy subsequent to NGS analysis, among them 75 received treatment according to NCCN guidelines, 9 off-protocol and 7 received immunotherapy due to high tumor mutation burden found on NGS analysis; Group D received targeted therapy due to standard molecular tests, as PCR, IHC and FISH performed prior to NGS. Median Overall survival (OS) is summarized in the Table (p = 0.0278).Table: (Abstract 145P)Overall Survival

      Total Cohort (n = 234)Group A 46% (108/234)Group B 5.5% (13/234)Group C 39% (91/234)Group D 9.5% (22/234)
      Median OS20.9 months (95% CI: 19.0–28.7)17.8 months (95% CI: 13.1–24.2)10.8 months (95% CI: 4.1–NA)25.7 months (95% CI: 19.9–41.7)37.7 months (95% CI: 26.7–NA)


      Conclusions:
      This study evaluates the clinical impact of comprehensive NGS testing by demonstrating the survival advantage of patients with actionable targets discovered through NGS. Comprehensive tissue and liquid-based NGS have revealed targeted treatment options for a significant number of patients. Overall Survival of patients treated with tailored therapy subsequent to NGS analysis was positively impacted in comparison to patients without an actionable target, only exceeded by patients who received targeted treatment subsequent to upfront standard molecular tests.

      Clinical trial identification:


      Legal entity responsible for the study:
      Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel.

      Funding:
      Has not received any funding

      Disclosure:
      S. Geva: Travel grant from Teva Pharmaceuticals, Honorarium from Guardant Health. L.C. Roisman: Lectures fees: Roche, MSD, Pfizer, Astrazenca. M. Ilouze: Honorarium from Pfizer, MSD, Roche and Takeda. A. Zer: Personal fees from Roche, grants and personal fees from BMS, personal fees from AstraZeneca, personal fees from BI, outside the submitted work. N. Peled: Advisor & Honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.

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      146P - The clinical impact of comprehensive cfDNA genomic testing in lung cancer (ID 566)

      12:30 - 13:00  |  Author(s): A. Belilovski Rozenblum

      • Abstract
      • Slides

      Background:
      Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. Currently there is insufficient data in regard to the impact of cfDNA analysis on clinical decision making. In this study, we evaluated the clinical utility of cfDNA sequencing on treatment strategy and progression-free survival in non-small cell lung cancer (NSCLC) patients.

      Methods:
      In this retrospective study, data was collected from files of 116 NSCLC patients monitored between the years 2014–2017 in Israel. Plasma samples from stage IIIb/IV NSCLC patients were analyzed by a commercial test (Guardant 360), using hybrid capture, single molecule barcoding and massively parallel paired-end synthesis to sequence a targeted gene panel. This test allows the detection of somatic alterations such as point mutations, indels, fusions and copy number amplifications.

      Results:
      116 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, male:female ratio was 1:1.7. 40% (47/116) were never-smokers, 83% (96/116) had adenocarcinoma. 41.4% (48/116) were tested before 1[st] line therapy (Group A), 34.5% (40/116) upon progression on chemotherapy or immunotherapy (Group B1) and 24.1% (28/116) upon progression on EGFR TKIs (Group B2). The most common genes were EGFR sensitizing mutations (25.9%, 30/116), MET amplifications and/or exon 14 skipping mutations or resistance point mutation (9.5%, 11/116) and EGFR T790M mutations (6.9%, 8/116). Clinical outcome of cfDNA analysis and targeted therapy for the entire cohort and for each group are summarized in the Table.Table: (Abstract 146P)Clinical Outcome of cfDNA Analysis and Targeted Therapy

      Total (n = 116)Group A (n = 48)Group B1 (n = 40)Group B2 (n = 28)
      Drug-associated actionable Mutations (On/Off Lable)65% (75/116)65% (31/48)52.5% (21/40)82% (23/28)
      Lung Cancer Related Actionable Mutations (NCCN guidelines)41% (48/116)31% (15/48)32.5% (13/40)71% (20/28)
      Tretmanet change (Impact on Decision)26% (30/116)23% (11/48)25% (10/40)32% (9/28)
      Response Evaluable93% (28/30)82% (9/11)100% (10/10)100% (9/9)
      Response not Evaluable7% (2/30)18% (2/11) Early cessation of treatment d/t toxicity0% (0/10)0% (0/9)
      Response Assessment (RECIST): CR4% (1/28)0% (0/9)0% (0/10)11% (1/9)
      Response Assessment (RECIST): PR39% (11/28)44% (4/9)30% (3/10)44% (4/9)
      Response Assessment (RECIST): SD32% (9/28)56% (5/9)20% (2/10)22% (2/9)
      Response Assessment (RECIST): PD25% (7/28)0% (0/9)50% (5/10)22% (2/9)
      Objective Response Rate43% (12/28)44% (4/9)30% (3/10)55.5% (5/9)
      Disease Control Rate75% (21/28)100% (9/9)50% (5/10)78% (7/9)
      Median Duration of Treatment5 months (6/28 ongoing)9 months (4/9 ongoing)3.5 months (0/10 ongoing)4 months (2/9 ongoing)
      Durable Disease Control Rate (over 4 months)43% (13/30)64% (7/11)20% (2/10)44% (4/9)
      Median PFS3.6 months7.3 months2.5 months3.3 months


      Conclusions:
      This study extends the evidence for clinical utility of comprehensive NGS testing by demonstrating durability of response to plasma-detected genomic alterations. cfDNA NGS changes treatment decisions in a significant number of patients in this retrospective study. It also has the potential to reduce undergenotyping of advanced NSCLC patients, while reducing costs and complications of biopsies, and facilitating more precise use of targeted therapy as well as immunotherapy.

      Clinical trial identification:


      Legal entity responsible for the study:
      Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel.

      Funding:
      Has not received any funding

      Disclosure:
      S. Geva: Travel grant from Teva Pharmaceuticals, Honorarium from Guardant Health. A. Dvir, L. Soussan-Gutman: Employee of Oncotest (subsidiary of Teva pharmaceuticals), the distributor of Guardant360 in Israel. L.C. Roisman: Lectures fees: Roche, MSD, Pfizer, Astrazenca. A. Zer: Personal fees from Roche, grants and personal fees from BMS, personal fees from AstraZeneca, personal fees from BI, outside the submitted work. N. Peled: Advisor & Honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.

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