No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.1 The CheckMate 901 trial evaluated whether combining nivolumab with standard-of-care chemotherapy was more effective than chemotherapy alone in treating patients with previously untreated inoperable or metastatic urothelial cancer.2 The results showed that the addition of nivolumab to chemotherapy led to improved overall and progression-free survival outcomes in these patients.
Platinum-based chemotherapy is the standard of care for previously untreated patients with unresectable or metastatic urothelial carcinoma. First-line cisplatin-based chemotherapy has shown a response in more than 40% of patients, with a median overall survival of approximately fifteen months. Unfortunately, durable responses with this treatment are uncommon. Nivolumab, an antibody directed against programmed death 1 (PD-1), is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma after previous platinum-based chemotherapy and as adjuvant treatment for high-risk muscle-invasive urothelial carcinoma after radical resection. Notably, phase II trials exploring cisplatin-based chemotherapy in combination with PD-1 blockade showed promise for the treatment of urothelial carcinoma. This article reports the results from the CheckMate 901 trial evaluating nivolumab plus gemcitabine–cisplatin compared with gemcitabine–cisplatin alone in patients with previously untreated unresectable or metastatic urothelial carcinoma.
In this phase III, multinational, open-label trial, patients with previously untreated unresectable or metastatic urothelial carcinoma were randomly assigned to receive either intravenous nivolumab (at a dose of 360 mg) plus gemcitabine–cisplatin (nivolumab combination) every three weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every four weeks for a maximum of two years, or to receive gemcitabine–cisplatin alone every three weeks for up to six cycles. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Safety and objective response were exploratory outcomes.
Six hundred and eight patients underwent randomisation (1:1). At a median follow-up of 33.6 months, the addition of nivolumab resulted in prolonged OS (HR for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; p=0.02) compared to chemotherapy alone, with a median OS of 21.7 vs.18.9 months in the combination and chemotherapy arms, respectively. PFS was also significantly improved with the nivolumab-combination therapy (HR for progression or death, 0.72; 95% CI, 0.59 to 0.88; p=0.001) compared to chemotherapy alone, with a median PFS of 7.9 vs. 7.6 months in the combination and chemotherapy arms, respectively. At the 12-month mark, PFS rates were reported at 34.2% and 21.8%, respectively. The overall objective response was 57.6% vs. 43.1% in patients receiving the combination or chemotherapy alone, respectively, with 21.7% vs. 11.8% of patients achieving a complete response (CR). The median duration of CR was 37.1 vs. 13.2 months. Grade ≥3 adverse events occurred in 61.8% vs. 51.7% of patients, respectively.
The combined treatment of nivolumab plus gemcitabine–cisplatin demonstrated markedly improved outcomes in individuals with previously untreated advanced urothelial carcinoma compared to gemcitabine–cisplatin alone.1
2. ClinicalTrials.gov ID NCT03036098. A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer. Accessed on 7 December 2023.