Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

By R. Motzer, K. Penkov, J. Haanen, B. Rini, L. Albiges, M. Campbell, B. Venugopal, C. Kollmannsberger, S. Négrier, M. Uemura and 18 more. New England Journal of Medicine, 2019

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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.)

Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine

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Citations in the corpus

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence (2020, methodology): “This combination approval was based on results showing significant improved median PFS compared with sunitinib on the JAVELIN Renal trial [76] (Category 2A).”
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy (2020, background): “The combination of PD-1/PD-L1 inhibitors with a CTLA-4 inhibitor has shown promise, as evidenced by the approval of nivolumab in combination with ipilimumab for the treatment of metastatic melanoma, advanced renal cell carcinoma and mismatch repair-deficient (dMMR) colorectal cancer.(44,45) In addit”
Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, result): “The results show that in 560 PD-L1 positive patients, the combination therapy significantly increased the objective response rates, there was little difference in side effects between the two groups during the treatment period [393].”