FDA Approves Adjuvant Pembrolizumab to Treat Post-Nephrectomy RCC

The FDA approved pembrolizumab (Keytruda) as an adjuvant treatment for patients with renal cell carcinoma (RCC) who are at an intermediate-high or high risk of recurrence following nephrectomy with or without resection of metastatic lesions.¹

Findings from the phase 3 KEYNOTE-564 trial (NCT03142334) supported the regulatory decision. In this study, patients who received pembrolizumab experienced significantly improved investigator-assessed disease-free survival (DFS) compared with patients who received placebo (HR, 0.68; 95% CI, 0.53-0.87; P = .0010). Median DFS has not yet been reached.

“Despite decades of research, limited adjuvant treatment options have been available for earlier-stage renal cell carcinoma patients who are often at risk for recurrence. In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence,” said Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School, in a press release.² Pembrolizumab represents the first immunotherapy approved to treat patients with renal cell carcinoma in the adjuvant setting.“With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients.”

Participants in the experimental arm of the KEYNOTE-564 trial were exposed to pembrolizumab for 11.1 months. During this time, the most serious adverse events (AEs), which occurred in 20% of patients receiving the agent, included acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis. Pembrolizumab induced fatal AEs in 0.2% of patients, including 1 case of pneumonia.

The AEs associated with drug discontinuation included alanine aminotransferase (1.6%), colitis, and adrenal insufficiency (1% each). Twenty-one percent of patients discontinued the drug due to an immune-related AE. Among all-grade AEs, the most common reactions in the experimental arm were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

Pembrolizumab is an immunotherapy and is associated with immune-related AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. In the event of a severe AE, the drug should be withheld, and corticosteroids should be administered if appropriate.

Dosing instruction for pembrolizumab advise 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months. Pembrolizumab is an injection administered intravenously.

“[Pembrolizumab] is foundational for the treatment of patients with certain advanced cancers, and this approval marks the fourth indication for [Pembrolizumab] in earlier stages of cancer,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories. “[Pembrolizumab] is now the first immunotherapy approved for the adjuvant treatment of certain patients with renal cell carcinoma. This milestone is a testament to our commitment to help more people living with cancer.”

Reference

• FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. FDA. News release. November 17, 2021. Accessed November 18, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma
• FDA approves Merck’s Keytruda (pembrolizumab) as adjuvant therapy for certain patients with renal cell carcinoma following surgery. Businesswire. Press release. November 18, 2021. Accessed November 2018, 2021. https://www.businesswire.com/news/home/20211118005576/en/FDA-Approves-Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-as-Adjuvant-Therapy-for-Certain-Patients-With-Renal-Cell-Carcinoma-RCC-Following-Surgery