-
Je něco špatně v tomto záznamu ?
Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study
TK. Choueiri, M. Eto, R. Motzer, U. De Giorgi, T. Buchler, NS. Basappa, MJ. Méndez-Vidal, S. Tjulandin, S. Hoon Park, B. Melichar, T. Hutson, C. Alemany, B. McGregor, T. Powles, V. Grünwald, B. Alekseev, SY. Rha, E. Kopyltsov, A. Kapoor, T....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, randomizované kontrolované studie, práce podpořená grantem
NLK
ProQuest Central
od 2000-09-01 do Před 2 měsíci
Nursing & Allied Health Database (ProQuest)
od 2000-09-01 do Před 2 měsíci
Health & Medicine (ProQuest)
od 2000-09-01 do Před 2 měsíci
Public Health Database (ProQuest)
od 2000-09-01 do Před 2 měsíci
- MeSH
- everolimus MeSH
- karcinom z renálních buněk * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * MeSH
- následné studie MeSH
- sunitinib MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. METHODS: This is a protocol-prespecified updated overall survival analysis (data cutoff March 31, 2021) of the open-label, phase 3, randomised CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy for renal cell carcinoma, including anti-vascular endothelial growth factor therapy, or any systemic investigational anticancer drug, were eligible for inclusion from 200 sites (hospitals and cancer centres) across 20 countries. Patients were randomly assigned (1:1:1) to receive lenvatinib (20 mg per day orally in 21-day cycles) plus pembrolizumab (200 mg intravenously every 21 days; lenvatinib plus pembrolizumab group), lenvatinib (18 mg per day orally) plus everolimus (5 mg per day orally; lenvatinib plus everolimus group [not reported in this updated analysis]) in 21-day cycles, or sunitinib (50 mg per day orally, 4 weeks on and 2 weeks off; sunitinib group). Eligible patients were at least 18 years old with a Karnofsky performance status of 70 or higher. A computer-generated randomisation scheme was used, and stratification factors were geographical region and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint was progression-free survival assessed by independent imaging review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). In this Article, extended follow-up analyses for progression-free survival and protocol-specified updated overall survival data are reported for the intention-to-treat population. No safety analyses were done at this follow-up. This study is closed to new participants and is registered with ClinicalTrials.gov, NCT02811861. FINDINGS: Between Oct 13, 2016, and July 24, 2019, 1417 patients were screened for inclusion in the CLEAR trial, of whom 1069 (75%; 273 [26%] female, 796 [74%] male; median age 62 years [IQR 55-69]) were randomly assigned: 355 (33%) patients (255 [72%] male and 100 [28%] female) to the lenvatinib plus pembrolizumab group, 357 (33%) patients (275 [77%] male and 82 [23%] female) to the sunitinib group, and 357 (33%) patients to the lenvatinib plus everolimus group (not reported in this updated analysis). Median follow-up for progression-free survival was 27·8 months (IQR 20·3-33·8) in the lenvatinib plus pembrolizumab group and 19·4 months (5·5-32·5) in the sunitinib group. Median progression-free survival was 23·3 months (95% CI 20·8-27·7) in the lenvatinib plus pembrolizumab group and 9·2 months (6·0-11·0) in the sunitinib group (stratified hazard ratio [HR] 0·42 [95% CI 0·34-0·52]). Median overall survival follow-up was 33·7 months (IQR 27·4-36·9) in the lenvatinib plus pembrolizumab group and 33·4 months (26·7-36·8) in the sunitinib group. Overall survival was improved with lenvatinib plus pembrolizumab (median not reached [95% CI 41·5-not estimable]) versus sunitinib (median not reached [38·4-not estimable]; HR 0·72 [95% CI 0·55-0·93]). INTERPRETATION: Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma. FUNDING: Eisai and Merck Sharp & Dohme.
Biostatistics Eisai Nutley NJ USA
Clinic for Urology and Clinic for Medical Oncology University Hospital Essen Essen Germany
Clinical Research Eisai Nutley NJ USA
Clinical Research Merck Rahway NJ USA
Department of BioMedical Sciences Queensland University of Technology Brisbane QLD Australia
Department of Hematology and Oncology AdventHealth Cancer Institute Orlando FL USA
Department of Medical Oncology Cross Cancer Institute University of Alberta Edmonton AB Canada
Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA USA
Department of Medical Oncology Texas Oncology Baylor Charles A Sammons Cancer Center Dallas TX USA
Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA
Department of Medicine University of Miami Sylvester Comprehensive Cancer Center Miami FL USA
Department of Onco urology P A Hertsen Moscow Cancer Research Institute Moscow Russia
Department of Oncology Barts Cancer Institute Queen Mary Institute of London London UK
Department of Oncology The Royal Free NHS Trust London England UK
Department of Urology Kyushu University Fukuoka Japan
Department of Urology University Hospital Ludwig Maximilian University of Munich Munich Germany
ICON Research South Brisbane QLD Australia
Interdisciplinary Department of Medicine University of Bari 'A Moro' Bari Italy
Medical Oncology Department Hospital Universitario Ramón y Cajal Madrid Spain
State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc23003913
- 003
- CZ-PrNML
- 005
- 20230425140952.0
- 007
- ta
- 008
- 230418s2023 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/S1470-2045(23)00049-9 $2 doi
- 035 __
- $a (PubMed)36858721
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Choueiri, Toni K $u Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu
- 245 10
- $a Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study / $c TK. Choueiri, M. Eto, R. Motzer, U. De Giorgi, T. Buchler, NS. Basappa, MJ. Méndez-Vidal, S. Tjulandin, S. Hoon Park, B. Melichar, T. Hutson, C. Alemany, B. McGregor, T. Powles, V. Grünwald, B. Alekseev, SY. Rha, E. Kopyltsov, A. Kapoor, T. Alonso Gordoa, JC. Goh, M. Staehler, JR. Merchan, R. Xie, RF. Perini, K. Mody, J. McKenzie, CG. Porta
- 520 9_
- $a BACKGROUND: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. METHODS: This is a protocol-prespecified updated overall survival analysis (data cutoff March 31, 2021) of the open-label, phase 3, randomised CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy for renal cell carcinoma, including anti-vascular endothelial growth factor therapy, or any systemic investigational anticancer drug, were eligible for inclusion from 200 sites (hospitals and cancer centres) across 20 countries. Patients were randomly assigned (1:1:1) to receive lenvatinib (20 mg per day orally in 21-day cycles) plus pembrolizumab (200 mg intravenously every 21 days; lenvatinib plus pembrolizumab group), lenvatinib (18 mg per day orally) plus everolimus (5 mg per day orally; lenvatinib plus everolimus group [not reported in this updated analysis]) in 21-day cycles, or sunitinib (50 mg per day orally, 4 weeks on and 2 weeks off; sunitinib group). Eligible patients were at least 18 years old with a Karnofsky performance status of 70 or higher. A computer-generated randomisation scheme was used, and stratification factors were geographical region and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint was progression-free survival assessed by independent imaging review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). In this Article, extended follow-up analyses for progression-free survival and protocol-specified updated overall survival data are reported for the intention-to-treat population. No safety analyses were done at this follow-up. This study is closed to new participants and is registered with ClinicalTrials.gov, NCT02811861. FINDINGS: Between Oct 13, 2016, and July 24, 2019, 1417 patients were screened for inclusion in the CLEAR trial, of whom 1069 (75%; 273 [26%] female, 796 [74%] male; median age 62 years [IQR 55-69]) were randomly assigned: 355 (33%) patients (255 [72%] male and 100 [28%] female) to the lenvatinib plus pembrolizumab group, 357 (33%) patients (275 [77%] male and 82 [23%] female) to the sunitinib group, and 357 (33%) patients to the lenvatinib plus everolimus group (not reported in this updated analysis). Median follow-up for progression-free survival was 27·8 months (IQR 20·3-33·8) in the lenvatinib plus pembrolizumab group and 19·4 months (5·5-32·5) in the sunitinib group. Median progression-free survival was 23·3 months (95% CI 20·8-27·7) in the lenvatinib plus pembrolizumab group and 9·2 months (6·0-11·0) in the sunitinib group (stratified hazard ratio [HR] 0·42 [95% CI 0·34-0·52]). Median overall survival follow-up was 33·7 months (IQR 27·4-36·9) in the lenvatinib plus pembrolizumab group and 33·4 months (26·7-36·8) in the sunitinib group. Overall survival was improved with lenvatinib plus pembrolizumab (median not reached [95% CI 41·5-not estimable]) versus sunitinib (median not reached [38·4-not estimable]; HR 0·72 [95% CI 0·55-0·93]). INTERPRETATION: Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma. FUNDING: Eisai and Merck Sharp & Dohme.
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a lidé středního věku $7 D008875
- 650 12
- $a karcinom z renálních buněk $7 D002292
- 650 _2
- $a everolimus $7 D000068338
- 650 _2
- $a následné studie $7 D005500
- 650 12
- $a nádory ledvin $7 D007680
- 650 _2
- $a sunitinib $7 D000077210
- 655 _2
- $a klinické zkoušky, fáze III $7 D017428
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a randomizované kontrolované studie $7 D016449
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Eto, Masatoshi $u Department of Urology, Kyushu University, Fukuoka, Japan
- 700 1_
- $a Motzer, Robert $u Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- 700 1_
- $a De Giorgi, Ugo $u Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy
- 700 1_
- $a Buchler, Tomas $u Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic
- 700 1_
- $a Basappa, Naveen S $u Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
- 700 1_
- $a Méndez-Vidal, María José $u Department of Medical Oncology, Hospital Universitario Reina Sofía, Maimonides Institute for Biomedical Research of Córdoba, Córdoba, Spain
- 700 1_
- $a Tjulandin, Sergei $u Department of Clinical Pharmacology and Chemotherapy, N N Blokhin National Medical Research Center for Oncology, Ministry of Health of the Russian Federation, Moscow, Russia
- 700 1_
- $a Hoon Park, Se $u Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- 700 1_
- $a Melichar, Bohuslav $u Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
- 700 1_
- $a Hutson, Thomas $u Department of Medical Oncology, Texas Oncology-Baylor Charles A Sammons Cancer Center, Dallas, TX, USA
- 700 1_
- $a Alemany, Carlos $u Department of Hematology and Oncology, AdventHealth Cancer Institute, Orlando, FL, USA
- 700 1_
- $a McGregor, Bradley $u Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- 700 1_
- $a Powles, Thomas $u Department of Oncology, The Royal Free NHS Trust, London, England, UK; Department of Oncology, Barts Cancer Institute, Queen Mary Institute of London, London, UK
- 700 1_
- $a Grünwald, Viktor $u Clinic for Urology and Clinic for Medical Oncology, University Hospital Essen, Essen, Germany
- 700 1_
- $a Alekseev, Boris $u Department of Onco-urology, P A Hertsen Moscow Cancer Research Institute, Moscow, Russia
- 700 1_
- $a Rha, Sun Young $u Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea
- 700 1_
- $a Kopyltsov, Evgeny $u State Institution of Healthcare "Regional Clinical Oncology Dispensary", Omsk, Russia
- 700 1_
- $a Kapoor, Anil $u Division of Urology, Department of Surgery, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada
- 700 1_
- $a Alonso Gordoa, Teresa $u Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
- 700 1_
- $a Goh, Jeffrey C $u ICON Research, South Brisbane, QLD, Australia; Department of BioMedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia
- 700 1_
- $a Staehler, Michael $u Department of Urology, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- 700 1_
- $a Merchan, Jaime R $u Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
- 700 1_
- $a Xie, Ran $u Biostatistics, Eisai, Nutley, NJ, USA
- 700 1_
- $a Perini, Rodolfo F $u Clinical Research, Merck, Rahway, NJ, USA
- 700 1_
- $a Mody, Kalgi $u Clinical Research, Eisai, Nutley, NJ, USA
- 700 1_
- $a McKenzie, Jodi $u Clinical Research, Eisai, Nutley, NJ, USA
- 700 1_
- $a Porta, Camillo G $u Interdisciplinary Department of Medicine, University of Bari 'A Moro', Bari, Italy
- 773 0_
- $w MED00011558 $t The Lancet. Oncology $x 1474-5488 $g Roč. 24, č. 3 (2023), s. 228-238
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/36858721 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20230418 $b ABA008
- 991 __
- $a 20230425140937 $b ABA008
- 999 __
- $a ok $b bmc $g 1924522 $s 1190122
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 24 $c 3 $d 228-238 $e - $i 1474-5488 $m Lancet oncology $n Lancet Oncol. $x MED00011558
- LZP __
- $a Pubmed-20230418
