Phase II trial of gemcitabine + cisplatin + ipilimumab in patients with metastatic urothelial cancer.

Genitourinary Cancer
Session Type and Session Title: 
Oral Abstract Session B: Urothelial Carcinoma; Penile, Urethral, and Testicular Cancers
Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, and Testicular Cancers
Abstract Number: 


Poster Board Number: 
Poster Session B Board #B4
J Clin Oncol 34, 2016 (suppl 2S; abstr 357)
Matt D. Galsky, Noah M. Hahn, Costantine Albany, Mark T. Fleming, Alexander Starodub, Przemyslaw Twardowski, Sumanta K. Pal, Ralph J. Hauke, Guru Sonpavde, William K. Oh, Nina Bhardwaj, Sacha Gnjatic, Seunghee Kim-Schulze, Ziyue Liu; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Johns Hopkins University School of Medicine, Baltimore, MD; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; US Oncology Research, Virginia Oncology Associates, Hampton, VA; Indiana University Health Goshen Center for Cancer Care, Goshen, IN; City of Hope, Duarte, CA; Nebraska Cancer Specialists, Omaha, NE; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Mount Sinai Medical Center, New York, NY; Icahn School of Medicine at Mount Sinai, New York, NY; Columbia Univ, New York, NY; Division of Biostatistics, Indiana University, Indianapolis, IN

Abstract Disclosures


Background: Immune checkpoint blockade, with anti-PD-1/PD-L1 antibodies, has shown striking results in patients (pts) with mUC. While CTLA4 blockade has demonstrated pharmacodynamic effects in localized bladder cancer (Carthon, Clin Can Res, 2010), the role of CTLA4 blockade in mUC remains undefined. We hypothesized that chemotherapy may lead to immunogenic cell death, and other immunomodulatory effects, which could subsequently be exploited with the addition of ipilimumab. Methods: Pts with mUC received 2 cycles of gemcitabine + cisplatin (GC) alone followed by 4 cycles of GC + ipilimumab (GCIpi). The primary endpoint was % of patients alive at 1 year. Secondary endpoints included safety, objective response rate, and progression-free survival. Immune monitoring was performed at baseline, after GC alone, and after GCIpi. Results: 36 pts with mUC (median age 60; range: 33-80) were enrolled; KPS was 80%, 90% and 100% in 30%, 45%, and 25%; 58% had visceral metastases and 20% had liver metastases. Pts received a median of 5 cycles of GC (range: 1-6) and 3 doses of Ipi (range: 1-8). The most common grade 3-4 adverse events were neutropenia (36%), thrombocytopenia (19%), anemia (25%), hyponatremia (31%), thromboembolism (11%), and renal insufficiency (19%). The most common grade 3-4 immune-related adverse events were colitis (6%), hypophysitis (3%), hyperthyroidism (1%), and rash (1%). The objective response rate is shown in the Table. Median progression-free survival is 8 months (95% CI 6.2-9.8 months). Median follow-up is 10.4 months (range: 2.8-35.3 months). The primary endpoint analysis will be mature for the meeting. GC alone had no significant impact on circulating immune cell subsets; Ipi significantly expanded circulating CD4 and CD8 T cells. Conclusions: A phased schedule of GC plus immune checkpoint blockade was feasible in pts with mUC. Ipi induced immunomodulatory effects despite concurrent chemotherapy. Survival data are not yet mature. Ongoing analyses are exploring the impact of GC alone, and GCIpi, on antigen-specific T cell immunity and correlating such findings with “outlier” survival times. Clinical trial information: NCT01524991

Objective response rate.

N (%)
Overall23 (64%)
PR18 (50%)
CR5 (14%)
SD11 (31%)
PD2 (6%)