Adjuvant Pembrolizumab Improves Secondary Efficacy End Points in RCC

Toni K. Choueiri, MD, discusses results from the KEYNOTE-564 efficacy analysis of adjuvant pembrolizumab in renal cell carcinoma.

Toni K. Choueiri, MD, medical director of International Strategic Initiatives, director of the Lank Center for Genitourinary Oncology, senior physician and director of the Kidney Cancer Center at Dana-Farber Cancer Institute, and the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, discusses results from the KEYNOTE-564 (NCT03142334) efficacy analysis of adjuvant pembrolizumab (Keytruda) in renal cell carcinoma (RCC).

The double-blind phase 3 KEYNOTE-564 trial randomly assigned 994 patients with clear cell RCC to receive either pembrolizumab or placebo every 3 weeks following nephrectomy for up to 17 cycles. The primary end point was disease-free survival (DFS), which was reported at 24 months with a hazard ratio (HR) of 0.68 favoring pembrolizumab (95% CI, 0.53-0.87; P = .0010 [one-sided]).

Choueiri presented the results of key secondary end points at the 2022 American Society of Clinical Oncology Annual Meeting: time to first subsequent therapy (TFST), distant metastasis-free survival (DMFS), and time to second disease progression (PFS2). Overall survival data are not yet mature.

At 30.1-month median follow-up, there was an HR for DMFS of 0.63 favoring pembrolizumab (95% CI, 0.49-0.82). The TFST also favored pembrolizumab significantly, with a HR of 0.67 (95% CI, 0.50-0.90). The HR for PFS2 was 0.57 (95% CI, 0.39-0.85), showing longer time to disease progression after receiving subsequent therapy. The median was not reached for these end points, but they are consistent with the benefit to DFS.


0:08 | For DMFS, there were 140 events for placebo and 95 for pembrolizumab. There was a difference of 9% absolute difference in the metastases with an HR of 0.63, a 37% decrease in that specific risk. The TFST, in terms of drug therapy, radiation therapy, surgery, no matter what you look at, the events were higher in placebo-treated patients. The hazard ratio was 0.67, so [there was] a 33% decrease in the risk. And the time to second disease progression, also called PFS2, is the time from randomization to progression on next-line therapy or any cause of death; here also in addition the HR was 0.57, so [there was] a 43% decrease in their risk of having time to second disease progression [with pembrolizumab].

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