FDA Approves Firstline Keytruda®, Inlyta® Combo for Kidney Cancer

The U.S. Food and Drug Administration approved pembrolizumab (Keytruda®) in combination with axitinib (Inlyta®) for the firstline treatment of advanced renal cell carcinoma (RCC). Pembrolizumab is an anti-PD-1 therapy and axitinib is a tyrosine kinase inhibitor.

The approval was based on the pre-specified interim analysis of the randomized, multicenter, open-label, phase III pivotal KEYNOTE-426 trial, which included 861 patients (median age = 62 years; range = 26-90 years) who had not received systemic therapy for advanced RCC. Patients were randomized 1:1 to receive pembrolizumab 200 mg intravenously every three weeks up to 24 months in combination with axitinib 5 mg orally twice daily (n=432) or sunitinib (Sutent®) 50 mg orally once daily for four weeks and then off treatment for two weeks (n=429).

Keytruda/Inlyta Improves Survival Versus Sutent

After a median follow-up of 12.8 months (range = 0.1-22 months), overall survival (OS) was significantly improved in the pembrolizumab/axitinib combination cohort compared to sunitinib, resulting in a 47% reduction in the risk of death (hazard ratio [HR] = 0.53; 95% CI, 0.38-0.74; P<0.0001). Estimated 12-month OS rates were 90% in the combination group (95% CI, 86-92) and 78% (95% CI, 74-82) in the sunitinib group. Median OS was not reached in either cohort.

Progression-free survival (PFS) was also significantly improved with pembrolizumab plus axitinib (HR=0.69; 95% CI, 0.57-0.84; P=0.0001). Median PFS was 15.1 months (95% CI, 12.6-17.7) with pembrolizumab and axitinib compared with 11.1 months (95% CI, 8.7-12.5) with sunitinib. The objective response rate was 59% (95% CI, 54-64) and 36% (95% CI, 31-40), respectively (P<0.0001).

Fatal adverse events (AEs) occurred in 3.3% of patients receiving pembrolizumab and axitinib. Serious AEs occurred in 40% of patients receiving pembrolizumab plus axitinib and included hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%).

The most common AEs resulting in discontinuation of pembrolizumab, axitinib, or both drugs were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common AEs associated with the combination therapy were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).