2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Validation of broad panel clinical sequencing-based genomic risk stratification in patients with advanced lung adenocarcinomas.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #436)
J Clin Oncol 37, 2019 (suppl; abstr 9113)
Author(s): Sam Whipple, Axel Martin, Michael Martinec, Kathryn Cecilia Arbour, Venkatraman E. Seshan, Gregory J. Riely, Gracy Crane, Ronglai Shen; Genentech, Inc., South San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; Roche Products Ltd., Welwyn, United Kingdom
Background: We recently established the ability of broad-panel clinical sequencing data to stratify overall survival of patients with advanced lung adenocarcinomas in a single institutional experience (Shen, Riely et al., JCO Precision Oncology 2019). Here we sought to assess its generalizability to a broader range of patients (including patients from multiple community and academic sites) using a different sequencing panel, with an integrated electronic health record and genomic database. Methods: We identified 2,779 next-generation sequencing-tested patients with advanced lung adenocarcinomas from the Flatiron-Foundation Medicine Clinico-Genomic database. A genomic risk model developed from the initial discovery cohort (n=1,054) was used to calculate a risk score for each patient in the validation cohort, scaled between 0 and 10, indicating the risk of cancer specific mortality. Results: Patients in the validation cohort were classified into four risk categories with median survival ranging from 37.6 months (95% CI: 32.9-43.8) in the low risk group (n=534) to 10.9 months (95% CI: 8.0-16.5) in the highest risk group (n=75), representing a hazard ratio of 3.0 (95% CI: 2.2-4.1) and closely matching the discovery cohort observations. A smaller proportion of patients were deemed high risk in the validation cohort (2.7% vs 10% in the discovery cohort). There were some differences in the frequencies of the most common genomic alterations between the validation and discovery cohorts, including TP53 (57.3% vs 55.1%), KRAS (32.8% vs 30%), EGFR (18.6% vs 29.4%) as well as overlapping STK11 and KEAP1 co-mutations (2.4% vs 10%). Conclusions: We demonstrate that a clinical tumor sequencing-based genomic risk stratification strategy can be applied broadly across cohorts and different sequencing panels and platforms, to improve the understanding of heterogeneity in clinical outcome for patients with metastatic lung adenocarcinomas and the mutation and co-mutational patterns that underlie such heterogeneity.