Phase III KEYNOTE-564 Trial Data Show Keytruda Improves Survival in Renal Cell Carcinoma

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Data from the Phase III KEYNOTE-564 trial show adjuvant treatment with Merck’s Keytruda (pembrolizumab) produced superior overall survival (OS) vs. placebo in patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions.¹

These data, presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium, show that at a median follow-up of 57.2 months [range, 47.9−74.5 months]), adjuvant Keytruda improved OS by 38% compared with placebo, which was the trial’s key secondary endpoint.

“For patients with renal cell carcinoma, up to 40% may experience recurrence following surgery, at which point there is a significantly lower chance of survival,” Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School, said in a press release. “Results from KEYNOTE-564 show that pembrolizumab as adjuvant therapy significantly improved overall survival by 38% compared to placebo, becoming the first ever Phase III adjuvant trial to show improved survival for renal cancer patients at risk of recurrence after surgery.”¹

Keytruda is an anti-PD-1 therapy that has been found to increase the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that may affect tumors and healthy cells.

The randomized, double-blind KEYNOTE-564 (NCT03142334) trial analyzed Keytruda in patients with RCC who underwent nephrectomy and with disease that is intermediate-high risk, high risk or M1 no evidence of disease. The trial’s primary endpoint was disease-free survival (DFS) as assessed by investigator review, with secondary endpoints of OS and safety.¹

Investigators randomly assigned 994 patients 1:1 to receive either Keytruda 200 mg intravenously on day one of each three-week cycle for up to 17 cycles or placebo. Among patients in the Keytruda cohort, the estimated OS rate at 48 months was 91.2% compared with 86.0% for patients in the placebo cohort, a benefit that was observed across key subgroups.

Data from an earlier pre-specified interim analysis showed that at a median follow-up of 24.1 months, Keytruda lowered the risk of disease recurrence or death by 32% compared with placebo. The third interim analysis showed a DFS benefit consistent with prior findings for adjuvant treatment with Keytruda in lowering the risk of disease recurrence or death by 28% compared with placebo.

In terms of safety, the findings were consistent with previously reported adverse events (AEs) associated with Keytruda with no new safety signals. Treatment-related AEs (TRAEs) were observed in 79.1% of patients (n=386) administered Keytruda compared with 53.0% of patients (n=263) administered placebo. Grade 3-4 TRAEs were recorded in 18.6% of patients administered Keytruda compared with 1.2% of patients administered placebo.

On January 12, 2024, the FDA approved Keytruda with chemoradiation for the treatment of patients with FIGO 2014 stage III to IVA cervical cancer. The approval was the third for Keytruda for the treatment of cervical cancer and the 39th overall approved indication for the drug in the United States.²

To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.

“The positive [OS] results from KEYNOTE-564 build upon the disease-free survival data, which supported approvals of Keytruda for this indication worldwide,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a press release. “This is the second Keytruda study to demonstrate a significant overall survival benefit in an earlier stage of cancer, and these new results add to the progress we’re making in earlier stages of disease.”¹

References

1. Merck’s KEYTRUDA® (pembrolizumab) Reduced the Risk of Death by 38% Versus Placebo as Adjuvant Therapy for Patients With Renal Cell Carcinoma (RCC) at an Increased Risk of Recurrence Following Nephrectomy. Merck. News release. January 27, 2024. Accessed January 29, 2024.

2. FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemoradiotherapy as Treatment for Patients With FIGO 2014 Stage III-IVA Cervical Cancer. Merck. News release. January 12, 2024. Accessed January 29, 2024. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-chemoradiotherapy-as-treatment-for-patients-with-figo-2014-stage-iii-iva-cervical-cancer/