The Food and Drug Administration (FDA) approved pembrolizumab plus axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Approval was based on KEYNOTE‑426 (NCT02853331), a randomised, multi-centre, open-label trial conducted in 861 patients who had not received systemic therapy for advanced RCC.

Patients were enrolled regardless of PD-L1 tumour expression status and were randomly allocated to receive either pembrolizumab 200 mg intravenously every 3 weeks in combination with axitinib 5 mg orally twice daily, or sunitinib 50 mg orally once daily for 4 weeks and then off treatment for 2 weeks.

Treatment continued until confirmed disease progression or unacceptable toxicity.

Pembrolizumab was received for maximum of 24 months.

The main efficacy measures were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review (RECIST 1.1.)

The trial demonstrated a statistically significant improvement in OS in a pre-specified interim analysis for patients on the pembrolizumab plus axitinib arm (HR 0.53; 95% CI: 0.38, 0.74; p<0.0001).

With deaths reported in 18 percent of patients, the median OS was not reached in either arm.

The 12-month OS rate was 90 percent in the pembrolizumab plus axitinib arm and 78 percent for those treated with sunitinib.

The trial also demonstrated a PFS improvement for patients receiving pembrolizumab plus axitinib (HR 0.69; 95% CI: 0.57, 0.84; p=0.0001).

Median PFS was 15.1 and 11.1 months for those receiving pembrolizumab plus axitinib vs. sunitinib, respectively. 

Grade 3 or 4 hepatotoxicity occurred in 20 percent of patients.

Hepatotoxicity resulted in permanent discontinuation of pembrolizumab or axitinib in 13 percent of patients.

The most common adverse reactions in > 20 percent of patients who received pembrolizumab plus axitinib were diarrhoea, fatigue/asthenia, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation. 

The recommended pembrolizumab dose for this indication is 200 mg every 3 weeks with axitinib 5 mg orally twice daily.

Source: The Food and Drug Administration (FDA)