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FDA Approves Combination Therapy for Advanced RCC
The FDA has approved the combination of pembrolizumab plus axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
This approval was based on the KEYNOTE-426 clinical trial in which 861 patients who had not received systemic therapy for advanced RCC were randomized to receive pembrolizumab 200 mg every 3 weeks for up to 24 weeks in combination with axitinib 5 mg twice daily or sunitinib 50 mg once daily for 4 weeks and then off treatment for 2 weeks. Therapy was continued until disease progression or unacceptable toxicity occurred.
The main efficacy measures were overall survival (OS) and progression-free survival (PFS), assessed via a blinded independent central review.
Pembrolizumab plus axitinib showed a statistically significant improvement in OS in a pre-specified interim analysis (hazard ratio [HR], 0.53; 95% CI, 0.38-0.74; P <.0001).
Deaths were reported for 18% of patients in the trial and the median OS was not reached in either treatment arm. The 12-month OS rates were 90% and 78% in the pembrolizumab plus axitinib and sunitinib arms, respectively.
Pembrolizumab plus axitinib also showed an improvement in PFS over sunitinib (HR, 0.69; 95% CI, 0.57-0.84; P = .0001), with median PFS rates of 15.1 months and 11.1 months, respectively.
Grade 3 or 4 hepatoxicity was reported in 20% of patients, and resulted in permanent discontinuation of pembrolizumab plus axitinib in 13% of patients. The most common (≥20%) adverse events observed with pembrolizumab plus axitinib were diarrhea, fatigue/asthenia, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation.—Janelle Bradley
Source: US Food and Drug Administration. FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma. Updated April 22, 2019. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm636395.htm. Accessed April 22, 2019
