Lenvatinib plus Pembrolizumab or Everolimus 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, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
P30 CA008748
NCI NIH HHS - United States
PubMed
33616314
DOI
10.1056/nejmoa2035716
Knihovny.cz E-resources
- MeSH
- Survival Analysis MeSH
- Programmed Cell Death 1 Receptor antagonists & inhibitors MeSH
- Quinolines administration & dosage adverse effects MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Everolimus administration & dosage adverse effects MeSH
- Phenylurea Compounds administration & dosage adverse effects MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Carcinoma, Renal Cell drug therapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms drug therapy mortality MeSH
- Antineoplastic Agents adverse effects 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
- Research Support, N.I.H., Extramural MeSH
- Comparative Study MeSH
- Names of Substances
- Programmed Cell Death 1 Receptor MeSH
- Quinolines MeSH
- Everolimus MeSH
- Phenylurea Compounds MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Protein Kinase Inhibitors MeSH
- lenvatinib MeSH Browser
- pembrolizumab MeSH Browser
- Antineoplastic Agents MeSH
- Sunitinib MeSH
BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels. CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
References provided by Crossref.org
Impact of Immunotherapy on Real-World Survival Outcomes in Metastatic Renal Cell Carcinoma
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ClinicalTrials.gov
NCT02811861