Chemo-Immunotherapy in Advanced Urothelial Cancer

Platinum-based multi-agent chemotherapy has been the standard of care for metastatic urothelial cancer for 40 years, with level 1 evidence supporting the use of cisplatin-based combination therapy. Two previous phase 3 studies testing immune checkpoint blockade in combination with either cisplatin- or carboplatin-based chemotherapy failed to demonstrate improvement in overall survival (OS).

Now, in a pharmaceutical-sponsored, multinational, open-label, phase 3 trial, investigators randomized patients with previously untreated metastatic urothelial cancer to receive either gemcitabine-cisplatin (GC) alone (every 3 weeks for 6 cycles) or GC plus nivolumab (every 3 weeks for 6 cycles followed by nivolumab every 4 weeks) until disease progression or up to 2 years. The primary outcome measures were OS and progression-free survival (PFS).

Eligible patients had metastatic urothelial cancer, good performance status, and glomerular filtration rate ≥60 mL/min. Prior neoadjuvant/adjuvant chemotherapy was permitted if more than 12 months had elapsed from therapy completion.

Among the 608 patients, median age was 65 years, 77% were male, and 53% had ECOG performance status 0. At a median follow-up of 33.6 months, OS was significantly longer with nivolumab/GC than with GC alone (median, 21.7 vs. 18.9 months; hazard ratio for death, 0.78; P=0.02), as was PFS (median, 7.9 vs. 7.6 months; HR, 0.72; P=0.001). The median duration of complete response was also longer in the nivolumab/GC arm (37.1 vs. 13.2 months). There were no unexpected toxicities; grade 3 or higher treatment-related adverse events were reported in 61.8% of the nivolumab/GC arm versus 51.7% of the GC arm.