Adjuvant pembrolizumab in non–clear cell renal cell carcinoma after nephrectomy: An international multicenter study.

473 Background: KEYNOTE-564 demonstrated that adjuvant pembrolizumab improves outcomes after nephrectomy for clear-cell renal cell carcinoma (RCC). Whether this benefit extends to non–clear cell RCC (nccRCC) remains uncertain. We evaluated the association between adjuvant pembrolizumab and outcomes in patients with nccRCC who underwent nephrectomy in a multicenter study. Methods: We conducted a retrospective multicenter cohort study at six international institutions. Eligible adults had nccRCC treated with nephrectomy and were classified by receipt of adjuvant pembrolizumab. The primary endpoints were disease-free survival (DFS), defined as the time from nephrectomy to the first radiographic or clinical recurrence, and overall survival (OS), defined as the time from diagnosis to death or last follow-up. Survival functions were estimated with the Kaplan–Meier method and compared between groups using the log-rank test. Estimates of median DFS and OS were calculated using the Kaplan–Meier method. Results: Patient characteristics are shown in Table 1. Among 90 patients, 15 (17%) received adjuvant pembrolizumab, and 75 (83%) were observed; age at diagnosis was 56.0 years (IQR 44.0–63.0; mean 52.9 ± 13.1) and 62.0 years (IQR 52.0–71.0; mean 59.6 ± 14.7) respectively. Recurrence occurred in 7/15 (46.7%) with pembrolizumab and 25/75 (44.6%) with observation. There was no significant difference in median DFS (p = 0.75) or OS (p = 0.89) between groups. Median DFS was 90.7 months (95% CI, 27.2–NR) with pembrolizumab vs 41.9 months (95% CI, 39.4–NR) with observation; median OS was not reached (95% CI, 65.1–NR) with pembrolizumab vs 52.4 months (95% CI, 44.4–NR) with observation. Conclusions: In this descriptive retrospective six-center cohort of nccRCC post-nephrectomy, adjuvant pembrolizumab did not demonstrate a DFS or OS advantage over observation. A larger multi-institutional cohort is in progress to refine effect estimates using richer clinical detail, with adjusted analyses and prespecified subgroup assessment. Baseline characteristics by treatment group. Characteristic Overall (n=90) Observation (n=75) Pembrolizumab (n=15) Sex (Male/Female), n (ratio) 58 / 32 (1.8:1) 48 / 27 (1.8:1) 10 / 5 (2:1) T1, n (%) 11 (12.2%) 10 (13.3%) 1 (6.7%) T2, n (%) 10 (11.1%) 10 (13.3%) 0 (0.0%) T3, n (%) 64 (71.1%) 52 (69.3%) 12 (80.0%) T4, n (%) 3 (3.3%) 2 (2.7%) 1 (6.7%) Papillary RCC, n (%) 41 (45.6%) 36 (48.0%) 5 (33.3%) Chromophobe RCC, n (%) 31 (34.4%) 27 (36.0%) 4 (26.7%) Unclassified RCC, n (%) 7 (7.8%) 6 (8.0%) 1 (6.7%) Xp11 translocation, n (%) 8 (8.9%) 4 (5.3%) 4 (26.7%)