Combined treatment with nivolumab (Opdivo), 1 mg/kg and ipilimumab (Yervoy), 3 mg/kg resulted in a 38% overall response rate in a study of platinum-pretreated metastatic urothelial cancer patients. That’s a higher response rate than previously reported results with any single-agent immunotherapy for metastatic bladder cancer.
“The current standard of care for patients who have failed frontline chemotherapy for metastatic bladder cancer is single-agent immunotherapy,” said study author Arlene O Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, Houston. The study was published in the Journal of Clinical Oncology (2019; 37:1608-16).
The FDA’s approval of single-agent programmed death 1 (PD-1) checkpoint inhibitors for bladder cancer in 2017 was big news in the cancer community, Dr. Siefker-Radtke said.
“We were all thrilled by having evidence of clinical activity, although the response rates are typically around 20% with a median survival of around 10 months. So, it’s clear that not all patients are benefiting from single-agent immune checkpoint inhibitor,” Dr. Siefker-Radtke said. “We need better ways of stimulating an immune response to cancer. And the combination of nivolumab with ipilimumab is showing evidence of an increase in immune response compared to what has been seen historically with single-agent immunotherapy.”
The PD-1 immune checkpoint inhibitor nivolumab, which blocks PD-1, is among the approved monotherapies for patients with locally advanced or metastatic bladder cancer who experience progression post chemotherapy. Ipilimumab blocks cytotoxic T-lymphocyte antigen-4. Researchers studying the combination have shown benefit in several types of tumors, according to the study.
Patients in this first combination immunotherapy trial for metastatic bladder cancer, called Checkmate 032, received either single-agent nivolumab or one of two immune checkpoint inhibitor combinations. One combination was 3 mg/kg nivolumab with 1 mg/kg ipilimumab; the other, 1 mg/kg nivolumab with a higher ipilimumab dose of 3 mg/kg.