CheckMate 901: Nivolumab Plus Gemcitabine-Cisplatin for Untreated mUC

Nivolumab plus gemcitabine-cisplatin demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) versus gemcitabine-cisplatin alone as first-line treatment of unresectable or metastatic urothelial carcinoma (mUC), according to results of the phase 3 CheckMate 901 trial presented as a late breaking abstract at the European Society for Medical Oncology Congress 2023.

While cisplatin-based chemotherapy has been considered the first-line standard of care for cisplatin-eligible patients with unresectable mUC for decades, previous attempts to improve upon this treatment have been unsuccessful.

Michiel S. Van der Heijden, MD, PhD, of the Netherlands Cancer Institute, reported the results for nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone in the global, open-label, randomized trial of 304 patients. Patients in the experimental arm received nivolumab (360 mg) plus gemcitabine-cisplatin every 3 weeks for up to 6 cycles followed by nivolumab (480 mg) every 4 weeks until disease progression, unacceptable toxicity, or a maximum of 2 years. Patients in the control arm received gemcitabine-cisplatin every 3 weeks for up to 6 cycles.

Patients were stratified based on PD-L1 status and liver metastasis. The primary end points were OS and PFS by blinded independent central review, and objective response rate (ORR) per blinded independent central review was an exploratory end point.

After a median follow-up of 33.6 months, OS (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; P=.0171) and PFS (HR, 0.72; 95% CI, 0.59-0.88; P=.0012) were significantly improved for patients receiving nivolumab plus gemcitabine-cisplatin.

ORR and complete response (CR) rates were 57.6% and 21.7% in the nivolumab arm, respectively, versus 43.1% and 11.8% in the control arm, respectively. Median duration of CR (95% CI) was 37.1 months (18.1-not estimable) versus 13.2 months (7.3-18.4), respectively.

Dr. Van der Heijden added that grade 3 or higher treatment-related adverse events occurred in 61.8% and 51.7% of patients, respectively. No new toxicities were reported from the nivolumab arm.

“Nivolumab plus gemcitabine-cisplatin is the first frontline concurrent checkpoint-inhibitor-plus-chemotherapy combination to improve OS in this setting,” they concluded. “These results support nivolumab plus cisplatin-based chemotherapy as a new standard of care for patients with mUC.”