ASCO 2016: Nivolumab Effective in Metastatic Bladder Cancer, Regardless of Tumor PD-L1 Status

Anti-programmed cell death protein 1 (PD-1) checkpoint inhibitor immunotherapy with nivolumab (Opdivo) is safe and effective in patients with metastatic bladder cancer refractory to prior lines of platinum-based chemotherapy, according to findings from the open-label, phase I/II CheckMate 032 trial, presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3-7, 2016, in Chicago (abstract 4501).

“In previously treated patients with metastatic urothelial cancer, for whom there is no standard of care, we provide the first evidence of substantial clinical activity with nivolumab-regardless of PD-L1 [PD-ligand 1 protein] expression,” said lead study author Padmanee Sharma, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“The median overall survival in this heavily pretreated group of patients-who had lots of visceral metastases-was 9.72 months (95% CI, 7.26-16.16 months),” Dr. Sharma reported. “The 12-month overall survival rate was 45.6%.”

Seventy-eight percent of the study’s 78 patients had visceral metastases, including 26% with liver metastases at baseline. More than half (53.8%) had two or three prior chemotherapy regimens, and 12.8% had undergone more than three prior treatment regimens.

The confirmed objective response rate (ORR) was 24.4% (95% CI, 15.3-35.4). Complete responses (CR) were seen in 6.4% of patients and partial responses (PR) in 17.9%. Stable disease was reported for 28.2% of patients, and progressive disease in 38.5%.

Median time to response was 1.48 months, Dr. Sharma said. “For complete and partial responses, first response was within six weeks of treatment in most cases,” she noted.

ORR was 26.2% (95% CI, 13.9-42.0) among patients with less than 1% of tumors expressing PD-L1, and 24.0% (95% CI, 9.4-45.1) among patients with 1% or more of tumors expressing PD-L1.

“Basically, we saw that PD-L1 status was irrelevant for response rate and didn’t matter in this cohort of patients,” Dr. Sharma reported.

Median progression-free survival (PFS) was 2.78 months (95% CI, 1.45-5.85 months).

Clinical responses were “durable over time” and nivolumab’s safety profile was “manageable and consistent with previous reports in other tumor types,” she said. Fatigue and pruritus were the most common treatment-related adverse events (TRAE), affecting 36% and 30% of patients overall (any grade).

Only 2.6% of study participants discontinued treatment because of drug toxicity, Dr. Sharma said. However, there were two treatment-related patient deaths: one due to thrombocytopenia and one associated with pneumonitis.

Further development of this treatment for patients with bladder cancer is ongoing in the phase II CheckMate 275 NCT02387996 study.

The trial was funded by Bristol-Myers Squibb.