The efficacy of those agents appeared similar to previous reports from phase II trials that enrolled cisplatin-ineligible patients regardless of PD-L1 expression status. The objective response rate was 27.9%, the median overall survival was 45 weeks, and the median failure-free survival was 16 weeks. However, grade ≥3 treatment-related toxicities appeared more common (31.7%) comparing with the cisplatin-ineligible first-line aUC cohorts of IMvigor210 and Keynote-052 trials (16% for each trial). The higher rate of treatment-related toxicities may be attributed to the fact that the platinum-ineligible patient population included in our study may be characterized as frailer than in these trials.
Hence, careful selection of platinum-ineligible patients for first-line PD1/L1 inhibitor therapy is warranted since this population remains poorly defined and may tolerate toxicities poorly. For example, a combination of biomarkers may warrant validation to facilitate patient selection, e.g. PD-L1 expression, tumor mutation burden (TMB), gene-expression subtyping, neutrophil/Lymphocyte ratio (NLR). Larger and prospective studies of new agents informed by predictive biomarkers are needed in platinum-ineligible aUC.
Guru Sonpavde: research grants from Boehringer-Ingelheim, Bayer, Onyx-Amgen, grants, and advisory board fees from Pfizer, advisory board for Genentech, advisory board for Novartis, research grants and advisory board for Merck, research grants and advisory board for Sanofi, advisory board and steering committee of trial for Seattle Genetics/Astellas, speaking fees from Clinical Care Options, grants, trial steering committee, advisory board and travel fees from Astrazeneca, writing fees from UpToDate, advisory board for Exelixis, advisory board and travel costs from Bristol-Myers-Squibb (BMS), research grants and advisory board Janssen, advisory board for Amgen, advisory board for Eisai, advisory board for NCCN, research grants from Celgene, speaking fees from Physicians Education Resource, Onclive, Research to Practice, Steering committee of trials sponsored by Bavarian Nordic, Debiopharm, QED.
Written by: Guru Sonpavde, MD, Bladder Cancer Director, Dana-Farber Cancer Institute, Associate Professor of Medicine, Harvard Medical School, Boston, MA
Read the Abstract