Published data show the PD-1 inhibitor induced strong antitumor activity in patients with both advanced clear cell renal cell carcinoma (ccRCC) and advanced non-ccRCC.
The PD-1 inhibitor pembrolizumab (Keytruda) demonstrated promising single-agent antitumor activity in patients with renal cell carcinoma (RCC), regardless of tumor histology, according to findings from the phase 2 KEYNOTE-427 study published in the Journal of Clinical Oncology.1,2
The single-arm KEYNOTE-427 study evaluated pembrolizumab monotherapy as frontline treatment in patients with advanced clear cell RCC (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Objective response rate (ORR) was the primary end point.
In patients with ccRCC, pembrolizumab induced an ORR of 36.4% and a disease control rate (DCR) of 58.2%. The ORR and DCR rates in the non-ccRCC cohort were 26.7% and 43%, respectively.
The ccRCC results included 110 patients with a median follow-up of 35.9 months (range, 29.5-40.3). The 36.4% ORR comprised 4 (3.6%) complete responses (CRs) and 36 (32.7%) partial responses (PRs). Over two-thirds (68.2%) of patients had a reductions in target lesion size, including a reduction of 60% or higher in 30.9% of patients.
The median duration of response was 18.9 months (range, 2.3-37.6+). Among the responders, 64.1% had a duration of response of at least 12 months.
The median progression-free survival (PFS) was 7.1 months and the median overall survival (OS) had not yet been reached. The 1- and 2-year OS rates were 88.2% and 70.8%, respectively.
Regarding safety and tolerability, there were no new safety signals compared with other research results with single-agent pembrolizumab in other tumor types. Overall, 30% of patients experienced grade 3 to 5 treatment-related adverse events, 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,” the authors wrote in their conclusion.
The findings for the non-ccRCC cohort included 165 patients, with a median follow-up of 31.5 months (range, 22.7-38.8). About three-fourths (71.5%) of the patients had confirmed papillary histology, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Over two-thirds (67.9%) of patients had intermediate or poor risk status, and 61.8% were PD-L1 positive (combined positive score ≥1).
The 26.7% ORR rate consisted of 11 CRs (6.7%) and 33 PRs (20%). The median duration of response was 29 months, with 59.7% of responses lasting for at least 12 months. Across histology subtypes, the ORR was 9.5% for chromophobe, 28.8% for papillary, and 30.8% for unclassified.
PD-L1 status appeared to affect response. The ORRs were 35.3% versus 12.1% among PD-L1–positive versus PD-L1–negative patients, respectively.
The median PFS and OS were 4.2 months and 28.9 months, respectively. The 2-year PFS and OS rates were 18.6% and 58.4%, respectively.
Toxicity data showed that there were no new safety signals compared with other research results with single-agent pembrolizumab in other tumor types. Across the cohort, 69.7% of patients experienced treatment-related adverse events. The most frequently occurring were pruritus (20.0%) and hypothyroidism (14.5%). The investigators considered 2 patient deaths (cardiac arrest and pneumonitis) on the trial to be related to study treatment.
“First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types,” the authors wrote in their conclusion.
Pembrolizumab is currently approved by the FDA for use in combination with axitinib for the first-line treatment of patients with advanced RCC.
1. McDermott DF, Lee J-L, Bjarnason GA, et al. Open-Label, single-arm phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced clear cell renal cell carcinoma [published online February 2, 2021]. J Clin Oncol. doi: 10.1200/JCO.20.02363
2. McDermott DF, Lee J-L, Ziobro M, et al. Open-label, single-arm, phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced non-clear cell renal cell carcinoma [published online February 2, 2021]. J Clin Oncol. doi: 10.1200/JCO.20.02365.