Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial

Matthew D. Galsky, Siamak Daneshmand, Sudeh Izadmehr, Edgar Gonzalez-Kozlova, Kevin G. Chan, Sara Lewis, Bassam El Achkar, Tanya B. Dorff, Jeremy Paul Cetnar, Brock O. Neil, Anishka D’Souza, Ronac Mamtani, Christos Kyriakopoulos, Tomi Jun, Mahalya Gogerly-Moragoda, Rachel Brody, Hui Xie, Kai Nie, Geoffrey Kelly, Amir HorwitzYayoi Kinoshita, Ethan Ellis, Yohei Nose, Giorgio Ioannou, Rafael Cabal, G. Kenneth Haines, Li Wang, Kent W. Mouw, Robert M. Samstein, Reza Mehrazin, Nina Bhardwaj, Menggang Yu, Qianqian Zhao, Seunghee Kim-Schulze, Robert Sebra, Jun Zhu, Sacha Gnjatic, John Sfakianos, Sumanta K. Pal

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes (ATM, RB1, FANCC and ERCC2) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. identifier: NCT03451331 .

Original languageEnglish
Pages (from-to)2825-2834
Number of pages10
JournalNature Medicine
Issue number11
StatePublished - Nov 2023


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