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ESMO 2017

ESMO 2017: Impact of Tumor Mutation Burden on Nivolumab Efficacy in Second-Line Urothelial Carcinoma Patients: Exploratory Analysis of the Phase II CheckMate 275 Study

Madrid, Spain (UroToday.com) Dr. Galsky and colleagues presented their results on the impact of tumor mutation burden on nivolumab efficacy as a second-line agent in patients with urothelial carcinoma. Nivolumab is a programmed death (PD)-1 inhibitor, which demonstrated efficacy in a single-arm phase II study in patients with metastatic or surgically unresectable urothelial carcinoma [1]. The objective of the current study was to explore the potential association between pretreatment tumor mutation burden and response to nivolumab as a post-hoc analysis of the CheckMate 275 study.

Among 139 patients with evaluable data, tumor DNA from pretreatment archival tumor tissue and matched whole blood samples were profiled by whole exome sequencing. Tumor mutation burden was defined as the total number of missense somatic mutations per tumor, and was evaluated as a continuous variable and by tertiles (missense count: high ≥167, medium 85–166, low <85). Cox proportional hazards models were used to explore the association between tumor mutation burden and progression-free survival (PFS) and overall survival (OS). Logistic regression was used to assess the role of tumor mutation burden and objective response rate (ORR). Tumor PD-ligand 1 (PD-L1) expression was assessed by Dako PD-L1 immunohistochemistry 28-8 assay and was categorized as
In conclusion, these exploratory findings suggest that increased tumor mutation burden may enrich for response to nivolumab and may provide complementary prognostic/predictive information beyond PD-L1. Further analyses in randomized trials are warranted to define the prognostic/predictive value of tumor mutation burden in the context of other biomarkers in urothelial patients treated with immunotherapy.

Speaker: Matthew D. Galsky, Memorial Sloan Kettering Cancer Center, New York, United States of America

Co-Authors: A. Saci (Princeton, United States of America) P. M. Szabo (Princeton, United States of America) A. Azrilevich (Princeton, United States of America) C. Horak (Princeton, United States of America) A. Lambert (Braine-l'Alleud, Belgium) A. Siefker-Radtke (Houston, United States of America) A. Necchi (Milan, Italy) P. Sharma (Houston, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

Reference:

1. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.