Pembrolizumab Plus Bevacizumab Safe, Effective for Metastatic RCC

Pembrolizumab combined with bevacizumab was shown to be safe and active in a study of patients with metastatic clear cell renal cell carcinoma (RCC; J Clin Oncol. 2020 Feb 25. Epub ahead of print).

Lead investigator Arkadiusz Z. Dudek, MD, PhD, HealthPartners Regions Cancer Care Center, St Paul, Minnesota, hypothesized that bevacizumab would increase the activity of pembrolizumab in patients with metastatic RCC.

Therefore, they conducted a single-arm, multi-site clinical trial of bevacizumab plus pembrolizumab in patients with metastatic clear cell RCC whose disease progressed following at least 1 systemic therapy (phase 1b) or who were treatment-naïve (phase 2).

The phase 1b study comprised a total of 13 patients (median age, 55 years) given pembrolizumab 200 mg plus bevacizumab 10 mg/kg or 15 mg/kg every 3 weeks, with no dose-limiting toxicities reported.

The 48 patients (median age, 61 years) in phase 2 of the study received pembrolizumab 200 mg and bevacizumab 15 mg/kg. The primary end point for phase 2 of the study was the overall response rate (ORR).

“With an 80% statistical power and a type I error probability of 0.1, 48 patients were to be accrued to detect an ORR of 42%,” the investigators said.

According to Dr Dudek et al, the primary end point was met, with an ORR of 60.9% (95% CI, 45.4%-74.9%), including 1 complete response (CR), 2 CRs in target lesions, 25 partial responses, and 18 responses of stable disease; 2 responses were deemed unevaluable.

The median progression-free survival was 20.7 months (95% CI, 11.3-27.4 months), and as of the median follow-up of 28.3 months, the median overall survival had not been reached.

Hypertension and proteinuria were the most frequently reported treatment-related grade 3 toxicities, and duodenal ulcer and hyponatremia were the 2 grade 4 toxicities that occurred.

“The combination of 200 mg of pembrolizumab and a 15 mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” Dr Dudek and colleagues concluded.—Hina M. Porcelli