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N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16.

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

Collaborators (146)

Bastos D, de Azevedo SJ, Marinho G, Murad AM, Schutz F, Zucca LE, Zylberberg R, Hotte S, Pouliot F, Soulières D, Wood L, Finek J, Holeckova P, Katolicka J, Kindlova E, Melichar B, Prausova J, Abadie-Lacourtoisie S, Bennamoun M, Chevreau C, Deville J, El Kouri C, Borchiellini D, Ferrero JM, Geoffrois L, Gross-Goupil M, Le Brun Ly V, Laplante M, Linassier C, Oudard S, Tartas S, Topart D, Tourani JM, Bedke J, Boegemann M, Lorch A, Merseburger A, Reichardt P, Retz M, Wirth M, Wuelfing C, Arkosy P, Horvath Z, Bodoky G, Csejtei A, Csoszi T, Geczi L, Revesz J, Ruzsa A, McCaffrey J, McDermott RS, Anai S, Eto M, Inoue T, Kato H, Kimura G, Kobayashi H, Kojima T, Masumori N, Matsubara A, Matsubara N, Matsumoto H, Mizuno R, Nakaigawa N, Nishimura K, Osawa T, Miyajima N, Oyama M, Sugimura Y, Takahashi M, Takano T, Tamada S, Tomita Y, Tsujihata M, Tsunemori H, Uemura H, Yamaguchi A, Langiewicz P, Szczylik C, Tomczak P, Wiechno P, Wojcik-Tomaszewska J, Pikiel J, Ziobro M, Alekseev B, Gafanov R, Karlov P, Matveev V, Nosov D, Shkolnik M, Bae WK, Lee HJ, Castellano Gauna D, Juan Fita M, Rodriguez-Vida A, Suarez C, Chang CH, Chang WC, Chuang CK, Chung HJ, Chang YH, Bondarenko I, Kryzhanivska A, Sakalo V, Shparyk Y, Stus V, Vynnychenko I, Hawkins R, Larkin J, Powles T, Wheater M, Amin A, Appleman L, Aragon-Ching J, Berg A, Dunder S, Cho D, Doshi G, Fruehauf J, Fung C, George S, Graham R, Hammers H, Brugarolas J, Kam A, Pfanzelter N, Kendall SD, Markus M, Cohn A, Matrana M, Nair S, Oyola R, Plimack E, Rini B, Ryan C, Schnadig I, Somer B, Sosman J, Carneiro B, Sumey C, Sundararajan S, Singh P, Bukowski R, Dutcher JP, Kim K, Kuzel TM.

Author information

1
From the Cleveland Clinic Taussig Cancer Institute, Cleveland (B.I.R.); Fox Chase Cancer Center, Philadelphia (E.R.P.); Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine (V.S.) and Dnipropetrovsk Medical Academy (I.B.), Dnipro, Sumy State University, Sumy Regional Oncology Center, Sumy (I.V.), and Ivano-Frankivsk National Medical University, Ivano-Frankivsk (A.K.) - all in Ukraine; the Russian Scientific Center of Roentgen Radiology (R.G.), Central Clinical Hospital with Outpatient Clinic (D.N.), and Hertzen Moscow Cancer Research Institute (B.A.), Moscow; the Christie NHS Foundation Trust, Manchester (R.H.), and Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London, London (T.P.) - all in the United Kingdom; Centre Hospitalier Universitaire (CHU) de Québec and Université Laval, Quebec, QC (F.P.), and CHU de Montréal, Montreal (D.S.) - both in Canada; Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic (B.M.); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (S.J.A.); Centre Antoine Lacassagne, Université Côte d'Azur, Nice (D.B.), and Hôpitaux Universitaires de Lyon, Lyon (S. Tartas) - both in France; Military Institute of Medicine, Warsaw, Poland (C.S.); Rocky Mountain Cancer Center, Colorado Springs, CO (M.M.); Adelaide and Meath Hospital and University College Dublin, Dublin (R.S.M.); the Department of Urology, Eberhard-Karls University Tübingen, Tübingen, Germany (J.B.); Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Osaka City University Hospital, Osaka, Japan (S. Tamada); MSD China, Beijing (Q.S.); Merck, Kenilworth, NJ (R.F.P., M.C.); and Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.B.A.).

Abstract

BACKGROUND:

The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear.

METHODS:

In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis.

RESULTS:

After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab-axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001). Median progression-free survival was 15.1 months in the pembrolizumab-axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001). The objective response rate was 59.3% (95% CI, 54.5 to 63.9) in the pembrolizumab-axitinib group and 35.7% (95% CI, 31.1 to 40.4) in the sunitinib group (P<0.001). The benefit of pembrolizumab plus axitinib was observed across the International Metastatic Renal Cell Carcinoma Database Consortium risk groups (i.e., favorable, intermediate, and poor risk) and regardless of programmed death ligand 1 expression. Grade 3 or higher adverse events of any cause occurred in 75.8% of patients in the pembrolizumab-axitinib group and in 70.6% in the sunitinib group.

CONCLUSIONS:

Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.).

PMID:
30779529
DOI:
10.1056/NEJMoa1816714

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