On April 19, 2019, the FDA accelerated the approval of pembrolizumab (Keytruda; Merck) plus axitinib (Inlyta; Pfizer) as first-line treatment of patients with advanced renal-cell carcinoma (RCC). Keytruda was previously approved as a single agent or in combination with other agents for many other indications and types of cancers.
This latest approval was based on the phase 3, randomized, open-label, KEYNOTE-426 clinical trial of 861 patients with clear-cell metastatic RCC who had not received systemic therapy for metastatic disease. The patients were randomized in a 1:1 ratio to pembrolizumab 200 mg every 21 days plus axitinib 5 mg twice daily or to monotherapy with sunitinib (Sutent) 50 mg once daily, for 28 days.
The 12-month overall survival (OS) rate was 89.9% in the combination arm versus 78.3% in the sunitinib arm. The median OS was not reached in either arm. In addition, pembrolizumab plus axitinib showed improvement in progression-free survival (PFS). The median PFS was 15.1 months with pembrolizumab plus axitinib versus 11.1 months with sunitinib monotherapy.
Grade 3 or 4 hepatotoxicity occurred in 20% of patients, leading to permanent discontinuation of pembrolizumab or axitinib in 13% of patients.
The most common (>20%) adverse effects with the combination regimen were diarrhea, fatigue, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.
