Post-nephrectomy pembrolizumab improves disease-free survival

First results of the phase 3 KEYNOTE 564 trial showed that adjuvant therapy with pembrolizumab after nephrectomy enhanced disease-free survival of patients treated for locoregional clear cell renal cell cancer (RCC).

Nephrectomy is the standard-of-care treatment for locoregional RCC. However, nearly half of the patients eventually experience disease recurrence after surgery which is associated with shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need.

The phase 3, randomised KEYNOTE 564 trial (NCT03142334) evaluates the effect of pembrolizumab versus placebo as adjuvant therapy for patients with RCC. The study enrolled 994 patients with histologically confirmed clear cell RCC (intermediate-high risk [pT2, grade 4, or sarcomatoid, N0 M0; or pT3, any grade, N0 M0], high risk [pT4, any grade, N0 M0; or pT any stage, any grade, N+ M0], or M1 NED [no evidence of disease after primary tumour + soft tissue metastases completely resected ≤1 year from nephrectomy]). Participants were randomised 1:1 to pembrolizumab (200 mg every 3 weeks for 1 year) or placebo. The primary endpoint was disease-free survival in all randomised patients. Overall survival was a key secondary endpoint, as well as safety/tolerability. Dr Toni Choueiri (Dana-Farber Cancer Institute, MA, USA) presented the results of the first interim analysis of KEYNOTE 564 [1].

At a median follow-up of 24.1 months, the primary endpoint of disease-free survival was met (median not reached for both arms, HR 0.68; P=0.001; see Figure). The estimated disease-free survival rate at 24 months was 77.3% versus 68.1% in the pembrolizumab and placebo arm, respectively. Overall survival data are not yet mature.

Figure: Disease-free survival in the intention-to-treat population of KEYNOTE 564 [1]



All-cause adverse events were observed in 470 patients (96.3%) treated with pembrolizumab and 452 patients (91.1%) treated with placebo. Grade 3-5 all-cause adverse events occurred in 158 patients (32.4%) with pembrolizumab and 88 patients (17.7%) with placebo.

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   1. Choueiri TK, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: Randomized, double-blind, phase III KEYNOTE-564 study. Abstract LBA5, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202115 February, 2024