The phase 3 CheckMate 901 trial has established nivolumab in combination with chemotherapy as a viable frontline treatment for advanced urothelial carcinoma, significantly improving overall survival (OS) compared to chemotherapy alone. This combination, now FDA-approved, offers a new option for patients with unresectable or metastatic disease.
The CheckMate 901 trial randomized patients to receive either nivolumab or placebo in addition to cisplatin and gemcitabine chemotherapy, followed by maintenance with nivolumab or placebo. The primary endpoint was overall survival.
Survival Benefit
The trial demonstrated a median OS of 21.7 months (95% CI, 18.6-26.4) with nivolumab plus chemotherapy, compared to 18.9 months (95% CI, 14.7-22.4) in the chemotherapy-alone arm. This improvement aligns with historical data showing median OS lengths of approximately 18 to 20 months with traditional chemotherapy in this setting, according to Dr. Janaki Neela Sharma, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems.
Response Rates and Comparisons
The combination of nivolumab and chemotherapy achieved an overall response rate (ORR) of 57.6% (95% CI, 51.8%-63.2%). However, when indirectly compared with the enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) combination from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which showed an ORR of 67.7% (95% CI, 63.1%-72.1%), nivolumab plus chemotherapy appeared to elicit less robust responses. Dr. Sharma cautioned against direct cross-trial comparisons but noted that the data suggest enfortumab vedotin plus pembrolizumab may offer superior response rates.
Clinical Implications
The FDA approval of nivolumab plus cisplatin and gemcitabine in March 2024 was based on the CheckMate 901 trial results. This approval provides a new frontline treatment option for adult patients with unresectable or metastatic urothelial carcinoma. While enfortumab vedotin plus pembrolizumab is considered a preferred frontline treatment by many, nivolumab plus chemotherapy remains a valuable option, particularly in settings where the former is not suitable.
