Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial
-
Published:2023-10-02
Issue:11
Volume:29
Page:2825-2834
-
ISSN:1078-8956
-
Container-title:Nature Medicine
-
language:en
-
Short-container-title:Nat Med
Author:
Galsky Matthew D.ORCID, Daneshmand Siamak, Izadmehr SudehORCID, Gonzalez-Kozlova EdgarORCID, Chan Kevin G.ORCID, Lewis Sara, Achkar Bassam El, Dorff Tanya B., Cetnar Jeremy Paul, Neil Brock O., D’Souza Anishka, Mamtani Ronac, Kyriakopoulos ChristosORCID, Jun Tomi, Gogerly-Moragoda MahalyaORCID, Brody Rachel, Xie Hui, Nie Kai, Kelly Geoffrey, Horowitz Amir, Kinoshita Yayoi, Ellis Ethan, Nose Yohei, Ioannou Giorgio, Cabal Rafael, Del Valle Diane M., Haines G. Kenneth, Wang Li, Mouw Kent W., Samstein Robert M.ORCID, Mehrazin Reza, Bhardwaj NinaORCID, Yu Menggang, Zhao Qianqian, Kim-Schulze Seunghee, Sebra RobertORCID, Zhu JunORCID, Gnjatic SachaORCID, Sfakianos John, Pal Sumanta K.ORCID
Abstract
AbstractCystectomy 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. ClinicalTrials.gov identifier: NCT03558087.
Funder
V Foundation for Cancer Research Bristol-Myers Squibb U.S. Department of Health & Human Services | NIH | National Cancer Institute Foundation for the National Institutes of Health (FNIH)/Partnership for Accelerating Cancer Therapies
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference49 articles.
1. Marqueen, K. E. et al. Early mortality in patients with muscle-invasive bladder cancer undergoing cystectomy in the United States. JNCI Cancer Spectr. 2, pky075 (2018). 2. Grossman, H. B. et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N. Engl. J. Med. 349, 859–866 (2003). 3. Griffiths, G., Hall, R., Sylvester, R., Raghavan, D. & Parmar, M. K. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J. Clin. Oncol. 29, 2171–2177 (2011). 4. Flaig, T. W. et al. A randomized phase II study of coexpression extrapolation (COXEN) with neoadjuvant chemotherapy for bladder cancer (SWOG S1314; NCT02177695). Clin. Cancer Res. 27, 2435–2441 (2021). 5. Herr, H. W., Bajorin, D. F. & Scher, H. I. Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome. J. Clin. Oncol. 16, 1298–301 (1998).
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|