Regulatory Decision Summary for Keytruda

Authorization for the indication sought in this Supplemental New Drug Submission (SNDS) was based on interim results of an international, multi-centre, randomized, double-blind, placebo-controlled trial. Patients (n = 994) with renal cell carcinoma post-nephrectomy at intermediate-high or high risk of recurrence received either 200 mg Keytruda (n = 496) or placebo (n = 498) every three weeks up to 12 months (1 year, up to 17 cycles). The primary efficacy endpoint for the trial was disease-free survival with overall survival being investigated as a key secondary endpoint. At the pre-specified interim analysis (about a median time of 24 months from randomization), disease-free survival was significantly longer in patients treated with pembrolizumab compared to placebo. This difference was statistically significant with a hazard ratio for recurrence or death of 0.68 at a 95% confidence interval of 0.53 to 0.87 and p value of 0.0014 (one-sided). The most common adverse reactions (ADRs) reported in at least 20% of patients were fatigue (29.7%), diarrhea (25.4%), pruritus (22.7%, arthralgia (22.1%, and hypothyroidism (20.1%). Most of drug-related hypothyroidism and hyperthyroidism events (the known ADRs for pembrolizumab) were Grade 1 and Grade 2 in severity (none at Grade 4 or 5). The safety findings were consistent with the previously established safety profile for pembrolizumab given as a monotherapy (reference safety database, N = 2,799). Data for overall survival was immature at the time of this SNDS submitted as longer follow-up time is needed. A post-marketing commitment was requested to determine the effect on overall survival.

Overall, based on the evidence of statistically significant improvement in disease-free survival and an acceptable tolerability and safety profile consistent with the known safety profile of pembrolizumab as a monotherapy, the benefit/risk ratio is considered positive to support pembrolizumab as adjuvant treatment for RCC patients at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.

The recommended dose of the drug is Keytruda 200 mg every 3 weeks or 400 mg every 6 weeks (a dose regimen that has been approved previously as alternative dose of 200 mg every 3 weeks for clinical use of pmebrolizumab).

An updated Risk Management Plan (RMP) for Keytruda was reviewed by Health Canada and considered acceptable.

For further details about Keytruda, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.