Combination immunotherapy is producing response rates ranging from 26% to 38% among patients with metastatic bladder cancer in the early stages of a three-arm clinical trial presented at the 2016 Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland.
“Until the first, recent approval of immune checkpoint therapy, patients with bladder cancer have not had new treatment options for over 30 years. We're quickly moving from immune checkpoint monotherapy to immune checkpoint combination therapies to improve outcomes for patients with bladder cancer,” said study principal investigator Padmanee Sharma, MD, PhD, Professor of Genitourinary Medical Oncology and Immunology at The University of Texas MD Anderson Cancer Center.
In the randomized phase I/II CheckMate 032 trial, patients who progress after platinum-based chemotherapy received either the anti–PD-1 (programmed cell death protein 1) inhibitor nivolumab (Opdivo), or one of two combinations of nivolumab plus the CTLA4 inhibitor ipilimumab (Yervoy). One combination had a higher dose of ipilimumab, the other a higher dose of nivolumab, given every 3 weeks for four cycles, followed by nivolumab every 2 weeks. All patients were treated until disease progression or unacceptable toxicity.
Patients receiving the combination with the higher dose of ipilimumab had the highest objective response rate (38.5%), which is confirmed complete response (disappearance of tumors) plus confirmed partial response (at least a 30% shrinkage of tumors).
“These early results with the higher dose ipilimumab provide evidence for improved responses with combination immune checkpoint therapy, which is exciting news to help drive the field to develop and test combination treatment strategies as a new standard of care for patients with metastatic disease, as well as for patients with earlier stages of disease,” Dr. Sharma said.
Responses appear to be durable, with 70% and 80% of responding patients on the combinations still having ongoing responses at the time of database lock.
Dr. Sharma presented only the combination data at the SITC session. Single-agent nivolumab data were reported in a Lancet Oncology paper by Sharma et al last month.
For the higher-dose ipilimumab combination, 76.9% of patients had at least one treatment-related adverse event of any grade, 30.8% had grade 3–4 events, and 7.7% discontinued treatment. For the higher dose nivolumab combination, 84.6% of patients had an event, 31.7% had grade 3–4 events, and 13.5% stopped treatment. For nivolumab alone, 81.1% of patients had events, 22% had grade 3–4 events, and 3% had to discontinue treatment.
Median follow up was 15.2 months for the nivolumab group, 16.7 months for the higher-dose nivolumab group, and 7.8 months for the higher dose ipilimumab group.
Dr. Sharma said the trial sponsor expanded the higher-dose ipilimumab arm later in the course of the trial, which accounts for the lower patient accumulation and shorter follow-up. They had been exploring the two combinations in other trials and realized that response rates differed among them, she explained. She also advocated the change based on earlier immune monitoring research of presurgical bladder cancer treatment that showed higher-dose ipilimumab increases T cells that have high levels of the immune stimulating protein ICOS.
As a phase I/II clinical trial, CheckMate 032 is assessing antitumor activity and remains under way. The trial is funded by Bristol-Myers Squibb.
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