No pain, no gain.

Top Line: Thanks to the new wave of immune checkpoint inhibitors, platinum-refractory bladder cancer has a whole host of non-chemo options to turn to. 
The Study: While pembro is “preferred” as the only one with phase 3 data backing a survival advantage, you can find pretty much any PD-1 axis inhibitor on the market within the list of possible next-steps. What’s conspicuously absent, though, is that classic combo of ipi + nivo. Did someone just say Checkmate? The phase 2 Checkmate 032 trial randomized 274 patients with platinum-refractory urothelial carcinoma to two years of [1] single-agent nivo 3 mg/kg q2 weeks versus [2] combo nivo 3 mg/kg + ipi 1 mg/kg q3 weeks x 4 → nivo maintenance versus [3] nivo 1 mg/kg + ipi 3 mg/kg q3 weeks x 4 → nivo maintenance. Among other things, the results add credence to the observation that increasing the ipi dose usually means increasing the side effects, with rates of grade 3-4 toxicity of [1] 27%, [2] 31%, and [3] 39%. But it wasn’t for nought, with the primary endpoint of objective response occurring in [1] 26%, [2] 27%, and [3] 38% and median survival times of [1] 10, [2] 7 and [3] 15 months. Although the authors warn that between-trial comparisons should be interpreted “with caution,” they cautiously proceed to note outcomes in arm [3] compare favorably to those seen with pembro, which conferred a response rate of 21% and median survival of 10 months.
Bottom Line: Combo ipi + nivo is looking to stake a claim in the treatment of platinum-refractory bladder cancer, offering up unprecedented response rates at the cost of more toxicity. | Sharma, J Clin Oncol 2019


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