Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.

Michiel S. Van Der Heijden*, Guru Sonpavde, Thomas Powles, Andrea Necchi, Mauricio Burotto, Michael Schenker, Juan Pablo Sade, Aristotelis Bamias, Philippe Beuzeboc, Jens Bedke, Jan Oldenburg, Gurkamal Chatta, Yüksel Ürün, Dingwei Ye, Zhisong He, Begoña P. Valderrama, Ja Hyeon Ku, Yoshihiko Tomita, Jeiry Filian, Lily WangDaniela Purcea, Miraj Y. Patel, Federico Nasroulah, Matthew D. Galsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Background No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. Methods In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. Results A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P=0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P=0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. Conclusions Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 number, NCT03036098.)

Original languageEnglish
Pages (from-to)1778-1789
Number of pages12
JournalNew England Journal of Medicine
Issue number19
StatePublished - 9 Nov 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 Massachusetts Medical Society.


  • Genitourinary Cancer
  • Hematology/Oncology
  • Treatments in Oncology
  • Urology/Prostate Disease
  • Urology/Prostate Disease General


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