Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Academic Article uri icon

Overview

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.).

authors

  • Motzer, Robert John
  • Penkov, Konstantin
  • Haanen, John
  • Rini, Brian
  • Albiges, Laurence
  • Campbell, Matthew T
  • Venugopal, Balaji
  • Kollmannsberger, Christian
  • Negrier, Sylvie
  • Uemura, Motohide
  • Lee, Jae L
  • Vasiliev, Aleksandr
  • Miller, Wilson H
  • Gurney, Howard
  • Schmidinger, Manuela
  • Larkin, James
  • Atkins, Michael B
  • Bedke, Jens
  • Alekseev, Boris
  • Wang, Jing
  • Mariani, Mariangela
  • Robbins, Paul B
  • Chudnovsky, Aleksander
  • Fowst, Camilla
  • Hariharan, Subramanian
  • Huang, Bo
  • di Pietro, Alessandra
  • Choueiri, Toni K

publication date

  • February 16, 2019

Research

keywords

  • Antibodies, Monoclonal
  • Antineoplastic Combined Chemotherapy Protocols
  • Axitinib
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Programmed Cell Death 1 Receptor
  • Sunitinib

Identity

PubMed Central ID

  • PMC6716603

Scopus Document Identifier

  • 85062945683

Digital Object Identifier (DOI)

  • 10.1200/JCO.2018.36.6_suppl.578

PubMed ID

  • 30779531

Additional Document Info

volume

  • 380

issue

  • 12