Pembrolizumab effective as post-nephrectomy adjuvant therapy in clear cell renal cell carcinoma: LANCET

Updated results from the KEYNOTE-564 trial showed that pembrolizumab monotherapy can be used as a standard of care for patients with renal cell carcinoma as per a study that was published in The LANCET Oncology. 

Post-nephrectomy adjuvant treatment for renal cell carcinoma has shown no consistent benefit despite 30 years of clinical investigation. Patients having localized renal cell carcinoma with one or several high-risk features and those with resectable soft tissue metastases at diagnosis benefit from adjuvant therapy. Patients having clear cell renal cell carcinoma with an increased risk of recurrence showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery from the first interim analysis of the KEYNOTE-564 trial. Hence researchers conducted an additional 6 months of follow-up, to assess the longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. 

A multicentre, randomized, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial was performed at 213 hospitals and cancer centers in North America, South America, Europe, Asia, and Australia between June 30, 2017, and Sept 20, 2019. Adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence and having an Eastern Cooperative Oncology Group performance status of 0 or 1 were taken. All the participants had undergone nephrectomy 12 weeks or less before randomization and had not received previous systemic therapy for advanced renal cell carcinoma. Using central permuted block randomization, patients were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. They were further stratified by metastatic disease status as M0 vs M1. M0 was further stratified by ECOG performance status and geographical region. All participants and investigators involved in the study treatment administration were masked to the treatment group assignment. The primary endpoint was disease-free survival by investigator assessment in the intention-to-treat population. Safety was assessed in the safety population, comprising all participants who received at least one dose of pembrolizumab or placebo.

Key findings: 

• Out of 994 participants 496 received pembrolizumab and 498 received placebo.
• Median follow-up was 30·1 month.
• Disease-free survival was better with pembrolizumab compared with placebo.
• Median disease-free survival was not reached in either group.
• The most common all-cause grade 3–4 adverse events were hypertension and increased alanine aminotransferase in the pembrolizumab group, and hypertension in the placebo group.
• Serious adverse events attributed to study treatment occurred in 59 (12%) participants in the pembrolizumab group and one (<1%) participant in the placebo group.
• No deaths were attributed to pembrolizumab. 

Thus, the researchers concluded from the study that pembrolizumab monotherapy can be used as standard adjuvant care for participants with renal cell carcinoma with an increased risk of recurrence after nephrectomy.

To read the full article, click here: https://doi.org/10.1016/S1470-2045(22)00487-9 

Powles T, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(9):1133-1144.