Adjuvant Pembrolizumab Demonstrates Superior DFS Over Placebo in Post-Nephrectomy RCC

Roy Baynes, MD, PhD

Single-agent pembrolizumab (Keytruda) resulted in a significant improvement in disease-free survival (DFS) when used as an adjuvant treatment in patients with renal cell carcinoma following nephrectomy or nephrectomy and resection of metastatic lesions, meeting the primary end point of the phase 3 KEYNOTE-564 trial (NCT03142334).¹

Additionally, the toxicity profile of pembrolizumab proved to be consistent with what had previously been reported with the agent.

The trial will continue to examine the overall survival (OS) benefit achieved with the immunotherapy, as an important secondary end point. Data from the trial will be shared at an upcoming medical conference, according to Merck; the findings will also be presented to regulatory authorities.

“Since its first approval in RCC nearly 2 years ago, [pembrolizumab] has become an important first-line treatment option in combination with axitinib [Inlyta] for patients with advanced RCC,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, stated in a press release. “These new data are the result of our research to evaluate the role of [pembrolizumab] in helping patients with earlier stages of disease and are the first positive results for an anti–PD-1 therapy in the adjuvant treatment of patients with RCC.”

In the double-blind phase 3 trial, investigators examined single-agent pembrolizumab in the adjuvant treatment of patients with RCC who had intermediate-high risk, high-risk, or M1 no evidence of disease with a clear cell component who had undergone nephrectomy.

To be eligible for enrollment, patients had to have an ECOG performance status of 0 to 1 and acceptable organ function.² Patients could not have previously received systemic therapy for advanced disease. If they had undergone major surgery other than nephrectomy within 12 weeks before randomization, received previous radiotherapy, had pre-existing brain or bone metastatic lesions, or had residual thrombus following nephrectomy in the vena renalis or vena cava, they were excluded.

A total of 950 patients were enrolled to the trial. Participants were randomized to receive either intravenous pembrolizumab at 200 mg on day 1 of each 3-week cycle for up to 17 treatment cycles or placebo on day 1 of each 3-week cycle for up to 17 cycles.

The primary end point of the trial was DFS, with key secondary end points of OS and safety.

In the United States, Europe, and Japan, the PD-1 inhibitor has been approved for use in combination with axitinib in the frontline treatment of patients with advanced RCC based on data from the phase 3 KEYNOTE-426 trial (NCT02853331). Here, the combination was found to result in a significantly better overall response rate, PFS, and OS vs sunitinib (Sutent) in patients with advanced disease.³ Specifically, the doublet reduced the risk of death by 47% vs sunitinib (HR, 0.53; 95% CI, 0.38-0.74; P <.0001); the regimen also reduced the risk of progression of disease or death by 31% vs sunitinib (HR, 0.69; 95% CI, 0.57-0.84; P = .0001).

References

1. Merck’s KEYTRUDA (pembrolizumab) demonstrated superior disease-free survival (DFS) compared with placebo as adjuvant therapy in patients with renal cell carcinoma (RCC) following surgery. News release. Merck. April 8, 2021. Accessed April 8, 2021. https://bit.ly/3fREZGr
2. Safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy (MK-3475-564/KEYNOTE-564). ClinicalTrials.gov. Updated May 28, 2020. Accessed April 8, 2021. https://clinicaltrials.gov/ct2/show/NCT03142334
3. FDA approves Merck’s KEYTRUDA (pembrolizumab) in combination with Inlyta (axitinib) as first-line treatment for patients with advanced renal cell carcinoma (RCC). News release. Merck. April 22, 2019. Accessed April 8, 2021. https://bit.ly/3wCYmJa