Highly discriminating biomarkers of response to cancer immunotherapies (CIT) remain elusive. Characterization of large real-world populations treated with CIT as part of routine care may enable better stratification.
Patients in the Flatiron Health Analytic Database with non-small cell lung cancer (NSCLC) who underwent comprehensive genomic profiling (CGP) by Foundation Medicine were included (n = 2139). CGP included >300 genes and tumor mutation burden (TMB), stratified into low (TMB-L; =20 mut/MB) tertiles (Johnson, CIR 2016). PD-L1 expression was obtained from results reported to clinicians from multiple labs (using varying antibodies). Genomic data was linked to de-identified electronic health record (EHR) data, from which nivolumab response was measured as overall response rate (ORR = SD, PR, or CR), median duration of therapy (mDOT), and median overall survival (mOS) from advanced diagnosis and from nivolumab initiation.
In patients treated with nivolumab (n = 444, 20.8%), TMB-H predicted longer mDOT than TMB-L/I (7.5 vs 4.6 months, p = 0.001), mOS from start of nivolumab treatment (median not reached vs 10 months, p
Real-world datasets combining clinical outcomes with genomic profiling may enable biomarker discovery in CIT. These data demonstrate the predictive power of TMB, which can augment and significantly improve on the currently approved PD-L1 expression as a predictor of CIT response. They may also enable discovery of novel biomarkers that can identify potential CIT responders among TMB-L populations.
Clinical trial identification
Legal entity responsible for the study
Foundation Medicine, Inc. and Flatiron Health, Inc.
G. Singal: Employee of Foundation Medicine, Inc., with equity and salary. P.G. Miller: Consultant with Foundation Medicine, Inc. V. Agarwala: Employee and shareholder of Flatiron Health, Inc. G. Li, L.A. Albacker, M.E. Goldberg, J. He, D. Bourque, D. Fabrizio, A. Parker, A. Guria, V.A. Miller, J.A. Elvin, J.S. Ross, P.J. Stephens: Employee and shareholder of Foundation Medicine, Inc. A. Gossai, S. Frank, I. Ivanov, T. Caron, A. Abernethy: Employee and shareholder of Flatiron Health, Inc.