Upfront Nivolumab/Chemo Produces Durable Responses in Urothelial Carcinoma

Michiel S. Van der Heijden, MD, PhD, Netherlands Cancer Institute, Amsterdam, the Netherlands, discusses the methods, design, and findings of the phase 3 CheckMate 901 trial (NCT03036098) of concurrent frontline nivolumab (Opdivo) and gemcitabine/cisplatin followed by nivolumab maintenance therapy for the treatment of patients with previously untreated, metastatic or unresectable urothelial carcinoma.

According to Van der Heijden and at a median follow-up of 33.6 months, OS was longer with the nivolumab combination vs with gemcitabine/cisplatin alone (HR, 0.78; 95% CI, 0.63-0.96; P =.02). The median survival was 21.7 months with the addition of nivolumab (95% CI, 18.6-26.4) vs 18.9 months (95% CI, 14.7-22.4), respectively, with gemcitabine/cisplatin alone.

Further, progression-free survival (PFS) rates were also improved among those treated with the nivolumab combination vs those given gemcitabine/cisplatin alone (HR, 0.72; 95% CI, 0.59-0.88; P =.001), and the median PFS was 7.9 months and 7.6 months, respectively. Moreover, the 12-month PFS rates were 34.2% and 21.8% across arms, respectively.

Transcription:

0:09 | This study was for adult patients who were cisplatin-eligible who had previously untreated, resectable, or metastatic urothelial cancer with a performance status of 0 to 1. These patients, approximately 600 patients in total, were randomized to [gemcitabine/cisplatin] with or without nivolumab. The primary end points of the study were overall survival and progression-free survival. Final analysis was done after about 360 events, and the P value boundary was around 0.03.

0:47 | At final analysis, it turned out that CheckMate 901 met its primary end point of overall survival, so nivolumab plus gemcitabine/cisplatin significantly improved overall survival with a hazard ratio of 0.78. The other primary end point is progression-free survival, and this study also met its primary end point of progression-free survival with a hazard ratio of 0.72. I think the important interesting thing that we noted in this study is that we increased response with this therapy response occurred rapidly. We especially increased complete remissions, and these complete remission standards have very good duration of response. Our conclusion was that the regimen we used here is associated with deep, rapid, and durable responses, and that leads in the end to an overall survival benefit.

Reference

van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine-cisplatin in advanced urothelial carcinoma. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863