First-Line Pembrolizumab Demonstrates Antitumor Activity in ccRCC Patients

According to an open-label, phase II study, pembrolizumab monotherapy as a first-line treatment showed promising antitumor activity in treatment-naive advanced clear cell renal cell carcinoma (ccRCC) patients (J Clin Oncol. 2021 Feb 2:JCO2002363)

“Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma,” explained David F. McDermott, MD, Dana-Farber/Harvard Cancer Center, Boston, MA, and colleagues.

Patients received pembrolizumab 200mg every three weeks for 24 months or less. The primary end point was objective response rate (ORR) by RECIST. 

A total of 110 patients were included in this study, with the median time from enrollment to data cutoff being 35.9 months. The ORR was 36.4%, with four (3.6%) complete responses and 36 (32.7%) partial responses. A majority of patients (68.2%) saw a decrease in target lesions, with 30.9% seeing a reduction of 60% or higher. 

The median duration of response was 18.9 months, with most responders  (64.1%) achieving response 12 months or later (Kaplan-Meier). The median progression-free survival (PFS) was 7.1 months (95% CI, 5.6 to 11.0), while the median overall survival (OS) was not reached. However, the 12-month and 24-month OS rates were 88.2% and 70.8%, respectively. 

Adverse events (AEs) grade 3 or higher were reported in 30.0% of patients, with colitis and diarrhea being the most common.

“Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types,” concluded Dr McDermott et al.