FDA Approves Adjuvant Pembrolizumab to Treat Post-Nephrectomy RCC

Pembrolizumab represents the first immunotherapy approved to treat patients with renal cell carcinoma in the adjuvant setting.

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; = .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.”

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