Phase 2 trial of gemcitabine plus nivolumab with carboplatin or oxaliplatin for metastatic urothelial carcinoma in cisplatin-ineligible patients

In cancer models, oxaliplatin can sensitize tumors to immune checkpoint blockade. A multicenter, randomized phase 2 trial compared gemcitabine-nivolumab plus oxaliplatin or carboplatin in cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). Forty-nine patients were randomized to gemcitabine-nivolumab-oxaliplatin (n=24) or gemcitabine-nivolumab-carboplatin (n=25) for up to 6 cycles, followed by nivolumab monotherapy. The primary endpoint was objective response rate (ORR). The ORR was 69.6% (95% CI 48-87) in the carboplatin arm versus 33.3% (15-57) in the oxaliplatin arm; median overall survival was 24.74 months versus 16.43 months, respectively (HR 1.99; p=0.07). Exploratory biomarker analyses revealed sustained adaptive immune activation in the carboplatin arm and features suggestive of tumor-promoting inflammation in the oxaliplatin arm. The authors conclude that oxaliplatin-based chemo-immunotherapy, versus carboplatin-based chemo-immunotherapy, did not yield a higher response rate, challenging assumptions based on preclinical data.