Dr Tripathi on the Use of Frontline Nivolumab/Chemotherapy in Urothelial Carcinoma

Abhishek Tripathi, MD, genitourinary medical oncologist, City of Hope, discusses key data from the phase 3 CheckMate 901 trial (NCT03036098) evaluating concurrent nivolumab (Opdivo) plus chemotherapy in metastatic or unresectable urothelial carcinoma, highlighting its clinical significance in the frontline setting.

The randomized, open-label trial assessed overall survival (OS) and progression-free survival (PFS) outcomes using nivolumab in combination with chemotherapy vs chemotherapy alone in cisplatin-eligible patients with previously untreated, metastatic or unresectable urothelial carcinoma, Tripathi reports. A total of 608 patients were included in the study and were randomly assigned in a 1:1 ratio to receive either nivolumab with gemcitabine/cisplatin followed by nivolumab maintenance therapy or standard gemcitabine/cisplatin alone.

Data from the phase 3 trial were presented at the 2023 ESMO Congress, showing that the nivolumab combination was shown to significantly increase both OS and PFS compared with chemotherapy alone, Tripathi states. The median OS was 18.9 months (95% CI, 14.7-22.4) with chemotherapy alone vs 21.7 months (95% CI, 18.6-26.4) in the combination group (HR, 0.78; 95% CI, 0.63-0.96; P = .0171), he details. Additionally, the median PFS was 7.9 months (95% CI, 6.1-7.8) with the nivolumab combination compared with 7.6 months (95% CI, 6.1-7.8 with chemotherapy alone (HR, 0.72; 95% CI, 0.59-0.88; P = .0012).

This trial represents one of the first studies to demonstrate a survival benefit with the combination of cisplatin-based chemotherapy and immunotherapy in the frontline setting for cisplatin-eligible patients with urothelial carcinoma, Tripathi emphasizes. However, the study faces challenges in the context of other combination studies reporting similar outcomes, he notes. It will be important to compare the regimen’s utilization to other novel, highly-effective combination therapies, such as enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda), Tripathi explains. However, in settings where access to novel agents is challenging or cost-effectiveness is crucial, the cisplatin-gemcitabine and nivolumab combination offers a reasonable treatment option for patients with metastatic disease, he concludes.