126P - The clinical impact of multiplex ctDNA gene analysis in lung cancer

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Lung and other Thoracic Tumours
Presenter Smadar Geva
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors S. Geva1, T. Twito2, A. Dvir2, L. Soussan-Gutman2, M. Ilouze3, L.C. Roisman3, E. Dudnik3, A. Zer3, R.B. Lanman4, N. Peled3
  • 1Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 69978 - Tel Aviv/IL
  • 2Teva Pharmaceutical Industries Ltd., Israel, Tel Aviv/IL
  • 3Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel, Petach Tikva/IL
  • 4Guardant Health, Inc., Redwood City, CA, San Francisco/US

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 360TM), 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 1st 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: 126P

Genetic alterations frequencies among groups A, B and B1

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
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
rn

rn

Response 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.