Pembrolizumab Offers Some Durable Responses in Advanced Urothelial Cancer

The PD-1 inhibitor pembrolizumab showed promising antitumor activity and acceptable safety in patients with advanced urothelial cancer, in a phase I trial.

The programmed death 1 (PD-1) inhibitor pembrolizumab showed promising antitumor activity and acceptable safety in patients with advanced urothelial cancer, according to a new phase I trial.

The study was part of the nonrandomized, multicohort, phase Ib KEYNOTE-012 basket trial of pembrolizumab. This portion of the study included a total of 33 patients with urothelial cancers of the bladder, renal pelvis, ureter, or urethra, with confirmed programmed death ligand 1 (PD-L1) expression in tumor cells or tumor stroma, treated at 8 hospitals in the United States and Israel. Patients received 10 mg/kg IV infusion of pembrolizumab every 2 weeks until progression, unacceptable toxicity, or through 24 months of treatment. Of those 33 patients, 27 were assessable for efficacy and the full cohort was assessable for safety. The results were published in Lancet Oncology.

“Several anti–PD-1/PD-L1 agents (eg, nivolumab, atezolizumab, durvalumab, and avelumab) have activity in urothelial cancer, thus showing that the PD-1 pathway represents an attractive target,” wrote study authors led by Elizabeth R. Plimack, MD, of Fox Chase Cancer Center in Philadelphia. Platinum-based chemotherapy is standard first-line treatment for this malignancy, but “there remains an unmet need for treatments of advanced urothelial cancer.”

After a median follow-up of 13 months, 7 of 27 patients achieved a response. Three of those were a complete response (11%), 4 were a partial response (15%), and another 4 (15%) had stable disease; 14 patients (52%) had progressive disease as their best response. The median time to response was 2 months, and the median response duration was 10 months; 3 of the responses lasted longer than 12 months.

The most common treatment-related adverse events included fatigue in 6 patients (18%), and peripheral edema in 4 patients (12%). Five patients experienced grade 3 treatment-related adverse events, and two of those required treatment discontinuation (one with myositis and rhabdomyolysis, and one with hypercalcemia). Six patients (18%) required a treatment interruption due to an adverse event, and 3 patients (9%) experienced 5 serious treatment-related adverse events. There were four deaths during the study, but none were deemed to be related to the study drug.

The median progression-free survival in the study was 2 months, with 15% of patients progression-free at 12 months. The median overall survival was 13 months, with a 50% overall survival rate at 12 months.

“The most important finding of this trial was the quality of the responses recorded in a subset of patients given single-agent pembrolizumab,” the authors wrote, noting that two patients remained in complete remission at the time of data cutoff. “These findings raise the possibility of durable disease control in patients with advanced urothelial cancer.”