On November 17, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of disease recurrence following nephrectomy or nephrectomy and resection of metastatic lesions.
Efficacy was evaluated in KEYNOTE-564, a multicenter, randomized (1:1), double-blind, placebo-controlled trial including 994 patients with intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease. Patients were randomly assigned to receive pembrolizumab at 200 mg intravenously every 3 weeks or placebo for up to 1 year until disease recurrence or unacceptable toxicity. The major efficacy outcome measure was investigator-assessed disease-free survival, defined as time to recurrence, metastasis, or death; an additional outcome measure was overall survival.
A statistically significant improvement in disease-free survival was demonstrated at a prespecified interim analysis, with 109 (22%) events in patients in the pembrolizumab arm and 151 (30%) events in those receiving placebo (hazard ratio = 0.68, 95% confidence interval = 0.53–0.87, P = .0010). Median disease-free survival was not reached in either arm. At the time of the disease-free survival analysis, overall survival data were not mature, with 5% deaths in the overall population.
The most common adverse reactions (≥ 20%) occurring in patients enrolled in KEYNOTE-564 were musculoskeletal pain, fatigue, rash, diarrhea, pruritus, and hypothyroidism.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence or unacceptable toxicity, or for up to 12 months.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Swissmedic. The application reviews may be ongoing at the other regulatory agencies. This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 3 weeks ahead of the FDA goal date. This application was also granted Priority Review.