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Clinical Trial
. 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

Brian I Rini  1 , Elizabeth R Plimack  1 , Viktor Stus  1 , Rustem Gafanov  1 , Robert Hawkins  1 , Dmitry Nosov  1 , Frédéric Pouliot  1 , Boris Alekseev  1 , Denis Soulières  1 , Bohuslav Melichar  1 , Ihor Vynnychenko  1 , Anna Kryzhanivska  1 , Igor Bondarenko  1 , Sergio J Azevedo  1 , Delphine Borchiellini  1 , Cezary Szczylik  1 , Maurice Markus  1 , Raymond S McDermott  1 , Jens Bedke  1 , Sophie Tartas  1 , Yen-Hwa Chang  1 , Satoshi Tamada  1 , Qiong Shou  1 , Rodolfo F Perini  1 , Mei Chen  1 , Michael B Atkins  1 , Thomas Powles  1 ; KEYNOTE-426 Investigators
Collaborators, Affiliations
Clinical Trial

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

Brian I Rini et al. N Engl J Med. .

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.).

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