Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
30779529
DOI
10.1056/nejmoa1816714
Knihovny.cz E-resources
- MeSH
- Intention to Treat Analysis MeSH
- Programmed Cell Death 1 Receptor antagonists & inhibitors MeSH
- Axitinib administration & dosage adverse effects MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Administration, Intravenous MeSH
- Single-Blind Method MeSH
- Carcinoma, Renal Cell drug therapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Kidney Neoplasms drug therapy mortality MeSH
- Antineoplastic Agents therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sunitinib adverse effects therapeutic use MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Programmed Cell Death 1 Receptor MeSH
- Axitinib MeSH
- Antibodies, Monoclonal, Humanized MeSH
- PDCD1 protein, human MeSH Browser
- pembrolizumab MeSH Browser
- Antineoplastic Agents MeSH
- Sunitinib MeSH
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.).
References provided by Crossref.org
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ClinicalTrials.gov
NCT02853331