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A. Zer



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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      126P - The clinical impact of multiplex ctDNA gene analysis in lung cancer (ID 476)

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

      • Abstract

      Background:
      Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. In this study, we evaluated the clinical utility of ctDNA sequencing on treatment strategy.

      Methods:
      In this retrospective study, data was collected from files of 109 NSCLC patients at the Thoracic Cancer Unit at Rabin Medical Center, Israel, between 2014-2017. Plasma samples from advanced non-small cell lung cancer (NSCLC) patients were analyzed by a commercial test (Guardant 360[TM]), using 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:
      109 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, 81% had adenocarcinoma. 39% (43/109) performed ctDNA analysis before 1[st] line therapy (Group A) and 61% (66/109) on progression (Group B), among them 42% (28/66) after progression on EGFR TKI (Group B1). ctDNA analysis yielded lung cancer related actionable mutations in 40% (44/109) of the patients; 32% (14/43) in group A and 45% (30/66) in group B; 71% (20/28) in group B1. Treatment decision was taken toward targeted therapy subsequent to NGS analysis in 27% of patients. 68 individual actionable genomic alterations were found (table).rnTable: 126PGenetic alterations frequencies among groups A, B and B1rn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      Group A: Upfront NGS (n = 43, 19 individual mutations)Group B: NGS on progression (n = 66, 49 individual mutations)Group B1: NGS on progression on EGFR TKIs (n = 28, 34 individual mutations)
      EGFR Sensitizing52% (10/19)EGFR Sensitizing45% (22/49)EGFR Sensitizing59% (20/34)
      MET16% (3/19)MET25% (12/49)EGFR T790M23% (8/34)
      ERBB210.5% (2/19)EGFR T790M16% (8/49)MET12% (4/34)
      BRAF V600E10.5% (2/19)RET6% (3/49)ERBB23% (1/34)
      RET10.5% (2/19)ERBB26% (3/49)ALK3% (1/34)
      rnrnALK2% (1/49)rnrn
      rnrnResponse assessment (RECIST) for 20 patients with evaluable response to targeted therapy showed complete response in 5% (1/20), partial response in 35% (7/20), stable disease in 25% (5/20) and progressive disease in 35% (7/20). Response rate was 20% (1/5) for group A, 47% (7/15) for group B, among them 67% (6/9) for group B1. Total objective response rate (ORR) was 40%.

      Conclusions:
      Comprehensive ctDNA testing revealed possible treatment options for 40% of patients analyzed. The highest impact was seen in the progressors on EGFR therapy. These positive results emphasize the utility of liquid biopsy analysis to guide clinicians to select the right therapy for the right patient.

      Clinical trial identification:


      Legal entity responsible for the study:
      Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.

      Funding:
      Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.

      Disclosure:
      S. Geva: Travel grant from Teva Pharmaceuticals. Honorarium from Guardant Health, Inc. T. Twito, A. Dvir, L. Soussan-Gutman: Employee of Oncotest (subsidiary of Teva pharmaceuticals), the distributor of Guardant360 in Israel. E. Dudnik: Consultant of BI. Honorary lectures for BI, Roche, AstraZeneca and MSD. R.B. Lanman: Employee with stock ownership in Guardant Health, Inc. N. Peled: Consultant for Pfizer, BI, Roche, AZ, MSD, BMS, Lilly, Novartis, and NovellusDx. All other authors have declared no conflicts of interest.