On May 14, 2019, the Food and Drug Administration approved avelumab (BAVENCIO, EMD Serono, Inc.) in combination with axitinib for first-line treatment of patients with advanced renal cell carcinoma (RCC).
Approval was based on JAVELIN Renal 101 (NCT02684006), a randomized, multicenter, open-label trial of avelumab plus axitinib in 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression. Patients were randomized to receive either avelumab 10 mg/kg intravenous infusion every 2 weeks in combination with axitinib 5 mg twice daily orally or sunitinib 50 mg once daily orally for 4 weeks followed by 2 weeks off until radiographic progression or unacceptable toxicity.
The main efficacy endpoints were progression-free survival (PFS), assessed by blinded independent central review using RECIST 1.1, and overall survival (OS) in patients with PD-L1-positive tumors. Secondary endpoints were PFS and OS in the total population. A statistically significant improvement in PFS was demonstrated in patients with PD-L1-positive tumors (HR 0.61; 95% CI: 0.48, 0.79; p=0.0001). A statistically significant improvement in PFS in the total population was also demonstrated (HR 0.69; 95% CI: 0.56, 0.84; p=0.0002) at interim analysis. Median PFS in the total population was 13.8 months for patients on the avelumab plus axitinib arm and 8.4 months for patients who received sunitinib. With a median overall survival follow-up of 19 months, OS data were immature with 27% deaths in the intent-to-treat population.
The most common adverse reactions of avelumab in combination with axitinib in ≥ 20% of patients with RCC were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Grade 3 or 4 hepatotoxicity occurred in 9% of patients and resulted in in permanent discontinuation of avelumab or axitinib in 7%. Major cardiac adverse events occurred in 7% of patients treated with the combination.
The recommended avelumab dose for advanced RCC is 800 mg as an intravenous infusion every 2 weeks in combination with axitinib 5 mg orally twice daily.
This application used the Assessment Aid pilot program. FDA granted this application priority review and Breakthrough Therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
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