FDA Approves Pembrolizumab plus Axitinib for Advanced Renal-Cell Carcinoma

Web Exclusives - FDA Updates, In the News, Renal-Cell Carcinoma

On April 19, 2019, the US Food and Drug Administration (FDA) approved a combination of pembrolizumab (Keytruda; Merck) plus axitinib (Inlyta; Pfizer) for the first-line treatment of patients with advanced renal-cell carcinoma (RCC), making it the first immunotherapy combination regimen approved for patients with this disease. This application was granted priority review and breakthrough therapy designation under the FDA’s accelerated review program and is the most recent in pembrolizumab’s recent string of approvals.

In the clinical trial on which this latest approval was based, the combination regimen of pembrolizumab plus axitinib led to a 47% reduction in the risk of death versus sunitinib. The data are from KEYNOTE 426, a multicenter, open-label, phase 3 trial of 861 patients with newly diagnosed or recurrent stage IV clear-cell RCC who had not received previous systemic treatment. Patients were randomized in a 1:1 ratio to intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles plus oral axitinib 5 mg twice daily every 3 weeks or oral sunitinib 50 mg once daily for the first 4 weeks of each 6-week cycle. Treatment continued until confirmed disease progression or unacceptable toxicity for a maximum of 24 months.

Overall survival (OS) and progression-free survival (PFS) were the major efficacy measures in the trial. An interim analysis showed that OS was significantly improved for patients in the pembrolizumab plus axitinib arm compared with those in the sunitinib arm. In the pembrolizumab plus axitinib arm, the 12-month OS rate was 90% (vs 78% in the sunitinib arm). Deaths were reported in 18% of patients. Median OS was not reached in either arm. PFS rates also showed improvement, with a median PFS of 15.1 months for patients receiving pembrolizumab plus axitinib compared with 11.1 months for those receiving sunitinib.

The most common adverse reactions in ≥20% of patients who received pembrolizumab plus axitinib included diarrhea, fatigue, hypertension, hypothyroidism, decreased appetite, hepatoxicity, palmar-plantar erythrodysesthesia, nausea, stomatitis, dysphonia, rash, cough, and constipation. Twenty percent of patients reported grade 3 or 4 hepatotoxicity, which resulted in permanent discontinuation of pembrolizumab or axitinib in 13% of patients.

This is the third approval this year for the immunotherapy agent pembrolizumab. Previously, it has been approved for use in the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors express PD-L1 TPS (Tumor Proportion Score) ≥50%; and within the past 2 weeks (April 11, 2019), it was approved for the first-line treatment of patients with metastatic NSCLC or stage III unresectable NSCLC for patients who are not candidates for definitive chemoradiation and whose tumors express TPS ≥1% and have no EGFR or ALK mutations.

Other indications for pembrolizumab include the treatment of melanoma, Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, cervical cancer, hepatocellular carcinoma, head and neck cancer, and Merkel-cell carcinoma.

Kidney cancer is the eighth most diagnosed cancer in the United States, and RCC is the most common type of adult kidney cancer; nearly 4% of all new cancer diagnoses are cancers of the kidney, according to the National Cancer Institute. Clear-cell cancer accounts for 80% of all RCC. The American Cancer Society estimates that more than 73,000 Americans will be diagnosed with kidney cancer in 2019.

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Last modified: July 22, 2021