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
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.