Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial
Language English Country England, Great Britain 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
33284113
DOI
10.1016/s1470-2045(20)30436-8
PII: S1470-2045(20)30436-8
Knihovny.cz E-resources
- MeSH
- Axitinib administration & dosage adverse effects MeSH
- Time Factors MeSH
- Progression-Free Survival MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Protein Kinase Inhibitors administration & dosage adverse effects MeSH
- Carcinoma, Renal Cell drug therapy mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms drug therapy mortality pathology MeSH
- Antineoplastic Agents, Immunological administration & dosage adverse effects MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Aged MeSH
- Sunitinib administration & dosage adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male 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
- Axitinib MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Protein Kinase Inhibitors MeSH
- pembrolizumab MeSH Browser
- Antineoplastic Agents, Immunological MeSH
- Sunitinib MeSH
BACKGROUND: The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma. METHODS: In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (≥18 years old) with treatment-naive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intention-to-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331. FINDINGS: Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30·6 months (IQR 27·2-34·2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35·7 months [95% CI 33·3-not reached] with sunitinib); hazard ratio [HR] 0·68 [95% CI 0·55-0·85], p=0·0003) and progression-free survival (median 15·4 months [12·7-18·9] vs 11·1 months [9·1-12·5]; 0·71 [0·60-0·84], p<0·0001). The most frequent (≥10% patients in either group) treatment-related grade 3 or worse adverse events were hypertension (95 [22%] of 429 patients in the pembrolizumab plus axitinib group vs 84 [20%] of 425 patients in the sunitinib group), alanine aminotransferase increase (54 [13%] vs 11 [3%]), and diarrhoea (46 [11%] vs 23 [5%]). No new treatment-related deaths were reported since the first interim analysis. INTERPRETATION: With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunitinib. These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma. FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
Adelaide and Meath Hospital Dublin Ireland; University College Dublin Dublin Ireland
Central Clinical Hospital With Outpatient Clinic Moscow Russia
Centre Antoine Lacassagne Université Côte d'Azur Nice France
Centre Hospitalier de l'Universitaire de Montréal Montréal QC Canada
CHU of Québec and Laval University Québec QC Canada
Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine Dnipro Ukraine
Fox Chase Cancer Center Philadelphia PA USA
Georgetown Lombardi Comprehensive Cancer Center Washington DC USA
Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
Merck and Co Kenilworth NJ USA
Merck Sharp and Dohme UK London UK
Osaka City University Hospital Osaka Japan
Palacky University Medical School and Teaching Hospital Olomouc Czech Republic
Russian Scientific Center of Roentgenoradiology Moscow Russia
Sumy State University Sumy Regional Oncology Center Sumy Oblast Ukraine
The Christie NHS Foundation Trust Manchester UK
University Hospital Eberhard Karls University Tübingen Tübingen Germany
References provided by Crossref.org
The Evolving Landscape of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma
ClinicalTrials.gov
NCT02853331
