Adjuvant pembrolizumab (Keytruda) improved overall survival (OS) compared with placebo in patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions, according to findings from the phase 3 KEYNOTE-564 trial.1
Merck (MSD), the developer of pembrolizumab, reported in a news release that an independent data monitoring panel determined that treatment with the PD-1 inhibitor led to a “statistically significant and clinically meaningful” survival benefit vs placebo. No new safety signals emerged with pembrolizumab. The company plans to share the OS data at a future medical meeting.
“As we continue to evaluate the potential of Keytruda in earlier stages of disease across multiple types of cancer, we hope to reduce disease recurrence and ultimately, improve overall survival outcomes,” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, stated in the news release. “These new results from KEYNOTE-564 are notable and mark the first time a therapy has demonstrated a statistically significant survival benefit compared to placebo in patients with RCC at a higher risk of recurrence following surgery, building on the positive disease-free survival findings from this study that led to approvals around the world for this Keytruda-based regimen.”
Based on previously reported data from KEYNOTE-564, the FDA approved pembrolizumab for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.2
The prior data showed that at a median follow-up of approximately 24 months, adjuvant pembrolizumab reduced the risk of disease recurrence or death by 32% vs placebo (HR, 0.68; P = .0010).3
In the double-blind, multicenter, phase 3 KEYNOTE-564 study (NCT03142334), investigators explored pembrolizumab vs placebo following nephrectomy in patients with clear cell RCC. Specifically, patients’ disease had to meet criteria that categorized them as high risk for recurrence, which included: pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0; pT4, any grade, N0, M0; any pT, any grade, N-positive, M0; or M1 with no evidence of disease after surgery.
Patients must have undergone nephrectomy within 12 weeks prior to randomization, could not have previously received systemic treatment, had to have an ECOG performance status of 0 or 1, and a tissue sample must have been obtainable for PD-L1 assessment.
All patients were randomized 1:1 to receive pembrolizumab (n = 496) at 200 mg every 3 weeks or placebo (n = 498) every 3 weeks, both for approximately 1 year. The primary end point of the trial was investigator-assessed DFS; secondary end points were overall survival (OS) and safety.
At 1 year, the estimated DFS rates were 85.7% and 76.2% with pembrolizumab and placebo, respectively. At 2 years, these rates were 77.3% and 68.1%, respectively.
The data cutoff date was December 14, 2020. Regarding safety, all-grade adverse effects (AEs) with pembrolizumab occurred in 96.3% of patients and in 91.1% of those on placebo; grade 3 to 5 AEs occurred in 32.4% and 17.7%, respectively. AEs led to death in 2 patients on pembrolizumab and in 1 patient on placebo.
Treatment-related AEs (TRAEs) occurred in 79.1% and 53.4% of pembrolizumab- and placebo-treated patients, respectively. A total 18.9% of patients on pembrolizumab had a grade 3 to 5 TRAE vs 1.2% of those on placebo. Notably, no TRAEs led to death in either arm. Overall, the safety profile was consistent with prior data on pembrolizumab.
1. KEYTRUDA® (pembrolizumab) Significantly Improved Overall Survival (OS) Versus Placebo as Adjuvant Therapy for Certain Patients With Renal Cell Carcinoma (RCC) Following Nephrectomy. Published online November 1, 2023. https://www.merck.com/news/keytruda-pembrolizumab-significantly-improved-overall-survival-os-versus-placebo-as-adjuvant-therapy-for-certain-patients-with-renal-cell-carcinoma-rcc-following-nephrectomy/
2. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. Published online November 17, 2021. Accessed November 17, 2021. https://bit.ly/3cmJeXs.
3. Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab vs placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: randomized, double-blind, phase 3 KEYNOTE-564 study. J Clin Oncol. 2021;39(suppl 15):LBA5.