On 17 November 2021, the US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck) for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Efficacy was evaluated in KEYNOTE-564 (NCT03142334), a multicentre, randomised (1:1), double-blind, placebo-controlled study in 994 patients with intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease. Patients were randomised to pembrolizumab 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 (DFS), defined as time to recurrence, metastasis, or death. An additional outcome measure was overall survival (OS).

A statistically significant improvement in DFS was demonstrated at a prespecified interim analysis, with 109 (22%) events in the pembrolizumab arm and 151 (30%) events in those receiving placebo (hazard ratio 0.68; 95% confidence interval 0.53, 0.87; p = 0.0010). Median DFS was not reached in either arm. At the time of the DFS analysis, OS data were not mature, with 5% deaths in the overall population.

The most common adverse reactions (≥20%) occurring in patients on this study were musculoskeletal pain, fatigue, rash, diarrhoea, pruritus, and hypothyroidism.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months.

Full prescribing information for Keytruda is available here.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, 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 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 granted priority review. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.