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FDA Approves Pembrolizumab Plus Axitinib for First-Line Treatment of Advanced Renal Cell Carcinoma

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On April 19, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) plus axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

KEYNOTE-426

Approval was based on KEYNOTE-426, a randomized, multicenter, open-label trial conducted in 861 patients who had not received systemic therapy for advanced RCC. Patients were enrolled regardless of programmed cell death-ligand 1 (PD-L1) tumor expression status, and were randomly assigned 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 and progression-free survival, assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors, version 1.1).

The trial demonstrated a statistically significant improvement in overall survival in a prespecified interim analysis for patients on the pembrolizumab-plus-axitinib arm (hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.38–0.74; P < .0001). With deaths reported in 18% of patients, the median overall survival was not reached in either arm. The 12-month overall survival rate was 90% in the pembrolizumab-plus-axitinib arm and 78% for those treated with sunitinib.

The trial also demonstrated a progression-free survival improvement for patients receiving pembrolizumab plus axitinib (HR = 0.69, 95% CI = 0.57–0.84; P = .0001). Median progression-free survival was 15.1 and 11.1 months for those receiving pembrolizumab plus axitinib vs sunitinib, respectively.  

Grade 3 or 4 hepatotoxicity occurred in 20% of patients. Hepatotoxicity resulted in permanent discontinuation of pembrolizumab or axitinib in 13% of patients. The most common adverse reactions in > 20% of patients who received pembrolizumab plus axitinib were diarrhea, 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 at 5 mg orally twice daily.

View the full prescribing information for pembrolizumab.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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