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N Engl J Med. 2019 Mar 21;380(12):1103-1115. doi: 10.1056/NEJMoa1816047. Epub 2019 Feb 16.

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

Author information

1
From Memorial Sloan Kettering Cancer Center (R.J.M.) and Pfizer (S.H.), New York; Private Medical Institution Euromedservice (K.P.) and Nonstate Health Institution Road Clinical Hospital-Russian Railways (A.V.), St. Petersburg, and the Moscow Scientific Research Oncology Institute, Moscow (B.A.) - all in Russia; the Netherlands Cancer Institute, Amsterdam (J.H.); the Cleveland Clinic, Cleveland (B.R.); Institut Gustave Roussy, Villejuif (L.A.), and Centre Léon Bérard, University of Lyon, Lyon (S.N.) - both in France; the University of Texas M.D. Anderson Cancer Center, Houston (M.T.C.); University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow (B.V.), and Royal Marsden NHS Foundation Trust, London (J.L.) - both in the United Kingdom; British Columbia Cancer Agency, Vancouver (C.K.), and Lady Davis Institute and Jewish General Hospital, McGill University, Montreal (W.H.M.) - both in Canada; Osaka University Hospital, Osaka, Japan (M.U.); University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea (J.L.L.); Macquarie University, Sydney (H.G.); Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna (M.S.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.B.A.); Department of Urology, University of Tübingen, Tübingen, Germany (J.B.); Pfizer, Cambridge (J.W., A.C.), and the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Boston (T.K.C.) - both in Massachusetts; Pfizer (M.M., A.P.) and Pfizer Italia (C.F.), Milan; Pfizer, San Diego, CA (P.B.R.); and Pfizer, Groton, CT (B.H.).

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.).

PMID:
30779531
DOI:
10.1056/NEJMoa1816047
[Indexed for MEDLINE]

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