KEYNOTE-564: OS Results From Adjuvant Pembrolizumab for Clear Cell RCC

After a median of approximately 57 months of follow-up, adjuvant pembrolizumab demonstrates a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo in participants with clear cell renal cell carcinoma (ccRCC) who are at increased risk of recurrence postsurgery, according to the results of a late-breaking abstract presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Previous data readouts of the randomized, multicenter, double-blind, phase 3 KEYNOTE-564 study showed that adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo after nephrectomy in patients with ccRCC who are at increased risk of recurrence.

Toni K. Choueiri, MD, FASCO, and colleagues reported long-term results from the third prespecified interim analysis.

In KEYNOTE-564, 994 patients with histologically confirmed ccRCC with or without sarcomatoid features, increased risk of recurrence, an Eastern Cooperative Oncology Group Performance Status of 0 or 1, prior nephrectomy and/or metastasectomy, and no prior systemic therapy for RCC were randomized (1:1) to pembrolizumab (200 mg) or placebo (intravenously every 3 weeks for ≥17 cycles). Patients received treatment for approximately 1 year or until disease recurrence, intolerable toxicity, or withdrawal of consent.

DFS by investigator assessment was the primary end point. OS was a key secondary end point, along with safety.

After a median time from randomization to data cutoff of 57.2 months, a statistically significant improvement in OS was observed with pembrolizumab compared with placebo (medians not reached; hazard ratio [HR], 0.62; 95% CI, 0.44-0.87; P=.0024).

Dr. Choueiri and colleagues reported that 55 OS events were observed in the pembrolizumab arm and 86 in the placebo arm, and the estimated OS rate at 48 months was 91.2% with pembrolizumab and 86.0% with placebo.

Additionally, OS benefit was observed across key subgroups, including patients with M0 disease (HR, 0.63; 95% CI, 0.44-0.90) or M1 with no evidence of disease (HR, 0.51; 95% CI, 0.15-1.75), with a PD-L1 combined positive score (CPS) <1 (HR, 0.65; 95% CI, 0.31-1.38) or PD-L1 CPS ≥1 (HR, 0.62; 95% CI, 0.42-0.91), and with presence of sarcomatoid features (HR, 0.69; 95% CI, 0.28-1.70) as well as absence of sarcomatoid features (HR, 0.57; 95% CI, 0.39-0.84).

The observed DFS benefit with pembrolizumab compared with placebo was consistent with prior interim analyses, researchers noted, and no new safety signals were observed.

“KEYNOTE-564 is the first phase 3 study to show improved survival with any adjuvant therapy in RCC,” they concluded, adding that “these results continue to support adjuvant pembrolizumab as a standard of care.”