Regulatory Decision Summary for Keytruda

Authorization was based on the results of a Phase 3 multi-centre, randomized, open-label controlled clinical trial. Flat dosing was based on a Phase 2 open label trial, with additional safety information coming from clinical experience with Keytruda in numerous other indications and with axitinib in the same disease setting.

Treatment-naïve patients (n=854) with advanced or metastatic renal cell carcinoma (RCC) with clear cell component received either Keytruda (200 mg intravenously every 3 weeks) combined with axitinib (5 mg twice daily, orally) or sunitinib (50 mg orally once daily for 4 weeks, followed by 2 weeks off, every cycle).

The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS). The pembrolizumab and axitinib combination treatment arm demonstrated clinically and statistically significant OS, PFS and overall response rate (ORR) results compared to the sunitinib arm.

The most common serious adverse drug reactions were: hyperthyroidism, hypothyroidism, diarrhea, nausea, stomatitis, asthenia, fatigue, mucosal inflammation, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, decreased appetite, arthralgia, proteinuria, dysphonia, palmar-plantar erythrodysaethesia syndrome, pruritus, rash and hypertension.

There are more risks associated with the combination therapy are than what was anticipated given the known risk profile of each drug in the combination. However, risk mitigation is achieved through close monitoring, especially of liver enzymes and function in this indication, and the appropriate use of systemic corticosteroid treatment when necessary, as described in the product monograph.

The recommended dose for this indication is 200 mg pembrolizumab administered intravenously over 30 minutes (up to 35 doses, approximately 24 months) in combination with axitinib 5 mg given orally twice daily.