Adjuvant Pembrolizumab Demonstrates Durable Survival Benefit for Post-Nephrectomy Patients With Clear Cell Renal Cell Carcinoma

Follow-up Analysis of Phase 3 KEYNOTE-564 Trial

Updated results from the 30-month follow-up analysis of the phase 3 KEYNOTE-564 trial confirmed the benefit seen from adjuvant pembrolizumab in disease-free survival for patients with renal cell carcinoma, following nephrectomy.

Before these trials, despite 30 years of clinical investigation, Thomas Powles, MD, Barts Cancer Institute, Queen Mary University of London, United Kingdom, and colleagues wrote, “post-nephrectomy adjuvant treatment for renal cell carcinoma has shown no consistent benefit… there is an unmet clinical need for randomized clinical trial-based evidence for efficacious and tolerable therapies in the adjuvant renal cell carcinoma setting.”

To meet this need, the multicenter, double-blind, phase 3 KEYNOTE-564 trial enrolled 994 patients who had undergone surgery for renal cell carcinoma with a clear cell component between June 30, 2017, and September 20, 2019. All patients were randomized on a 1:1 basis to receive either 200 mg pembrolizumab monotherapy (n = 496) or placebo (n = 498) once every 3 weeks, for a maximum of 17 cycles, or until disease progression. The primary end point was disease-free survival.

At the data cutoff date of June 14, 2021, for this updated analysis, the median duration of follow-up was 30.1 months. In the intention-to-treat population, disease free survival was better in the pembrolizumab group than in the placebo group (hazard ratio [HR] 0.63; 95% confidence interval [CI], 0.50 to 0.80). Median disease-free survival was not reached in either group. In the pembrolizumab group, the estimated proportion of patients alive and recurrence-free was 75.2% (95% CI, 70.8 to 79.1), compared to 65.5% (95% CI, 60.9 to 69.7) in the placebo group.

The most common grade 3/4 adverse events were hypertension (12% of the pembrolizumab group vs <1% in the placebo). There were no deaths attributed to treatment with pembrolizumab.

“To our knowledge, KEYNOTE-564 is the first positive study for adjuvant immunotherapy in renal cell carcinoma. The efficacy and safety update with 6 additional months of follow-up from the first interim analysis, as well as the spectrum of secondary and exploratory analyses, give further credence to the use of adjuvant pembrolizumab in this population,” Dr Powles and colleagues concluded.

Source:

Powles T, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(9):1133-1144. doi:10.1016/S1470-2045(22)00487-9