Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

Abstract

Background: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.

Methods: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety.

Results: A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups.

Conclusions: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).

Copyright © 2019 Massachusetts Medical Society.

Figures

Figure 1.. Progression-free Survival.

Progression-free survival among patients with programmed death ligand 1 (PD-L1)–positive tumors (Panel A) and among patients in the overall population (Panel B) is shown. NE denotes could not be estimated.

Figure 2.. Subgroup Analyses of Progression-free Survival and Best Percentage Change in Target Lesions among Patients with PD-L1–Positive Tumors.

Panel A shows the results of a subgroup analysis of progression-free survival among the patients with PD-L1–positive tumors. Eastern Cooperative Oncology Group (ECOG) performance-status scores range from 0 to 5,with higher numbers reflecting greater disability. Patients with favorable risk had a Memorial Sloan Kettering Cancer Center (MSKCC) score of 0, those with intermediate risk had a score of 1 or 2, and those with poor risk had a score of 3 or more. MSKCC risk scores are defined according to the number of the following risk factors present: a Karnofsky performance-status score of less than 80 (on a scale from 0 to 100, with lower scores indicating greater disability; patients with a performancestatus score of