The immune checkpoint inhibitor nivolumab reduced tumor burden in 24.4% of patients with metastatic bladder cancer, according to the early results of an ongoing multi-institutional clinical trial of the drug in patients with various solid tumor types.
Nivolumab blocks programmed cell death protein 1 (PD-1) by binding to the PD-1 ligands (PD-L1 and PD-L2). In May, atezoli zumab, which inhibits PD-L1 but not PD-L2, became the first drug to be approved by the U.S. Food and Drug Administration for the treatment of metastatic bladder cancer.
Because PD-L1 expression on tumor cells is considered a prognostic marker for response to PD-L1 inhibitors, a secondary endpoint of the nivolumab clinical trial was to see whether expression of the ligand on pretreatment tumor biopsy specimens correlated with response to nivolumab treatment. The primary endpoint of the trial was the objective response rate.
In the phase I portion of the trial, which has completed enrollment, patients with metastatic cancer receive nivolumab (3 mg/kg intravenously every 2 weeks) until their disease progresses or treatment is discontinued because of adverse events. The early results for the trial’s cohort of patients with metastatic bladder cancer, all of whom had previously received at least one line of platinum-based chemotherapy, were reported at the annual meeting of the American Society of Clinical Oncology in June.
The overall response rate was 24.4% for the 78 patients with metastatic bladder cancer treated in the phase I portion of the study: five patients had complete responses, and 14 had partial responses. An additional 22 patients had stable disease, and 30 patients experienced disease progression. Grade 3 or 4 side effects occurred in 16 patients, and two patients died of treatment-related effects.
“The response rate is better than we’ve seen for other potential secondline treatments, and nivolumab is really well tolerated, which is important because bladder cancer patients are a fragile group after front-line treatment with platinum chemotherapy,” said Padmanee Sharma, M.D., Ph.D., a professor in the Department of Genitourinary Medical Oncology and The University of Texas MD Anderson Cancer Center’s principal investigator for the trial.
Dr. Sharma added that there was no significant difference in response to nivolumab between patients whose tumors expressed PD-L1 and those whose tumors did not. “We can get good results without choosing to treat patients based on PD-L1 status,” Dr. Sharma said.
In the phase II portion of the trial, patients will receive nivolumab plus ipilimumab, which inhibits the immune checkpoint known as cytotoxic T lymphocyte–associated protein 4.
OncoLog, July 2016, Volume 61, Issue 7