First results of the phase 3 KEYNOTE 564 trial show that adjuvant therapy with pembrolizumab after nephrectomy enhances 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, randomized KEYNOTE 564 trial (NCT03142334) evaluates the effect of pembrolizumab versus placebo as adjuvant therapy for patients with RCC. A total of 994 patients with histologically confirmed clear cell RCC were enrolled in the study and randomized 1:1 to pembrolizumab (300 mg Q3W for 1 year) or placebo.

The primary endpoint was disease-free survival in all randomized 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 from 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=0.0010). The estimated disease-free survival rate at 24 months was 77.3% in the pembrolizumab arm versus 68.1% in the placebo arm. Overall, disease-free survival benefit was consistent across subgroups (age, sex, ECOG PS, PD-L1 status, metastatic staging).

Overall survival data are not yet mature. At data cut-off, only a total of 51 overall survival events were observed (18 in the pembrolizumab arm, 33 in the placebo arm). The estimated overall survival rate at 24 months was 96.6% with pembrolizumab versus 93.5% with placebo. 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. Dr Choueiri concluded that “KEYNOTE 564 is the first positive phase 3 study with a checkpoint inhibitor in adjuvant RCC, and these results support pembrolizumab as a potential new standard of care for patients with RCC in the adjuvant setting.” Additional follow-up is planned for the key secondary endpoint of overall survival.

  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. ASCO 2021 Virtual Meeting, abstract LBA5.

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