2026-04-18T06:12:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/119812024-11-01T01:14:15Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc chida, keigo author Xu, Rui-Hua author Passhak, Maria author Teng, Hao-Wei author Shergill, Ardaman author García-Alfonso, Pilar author 2024-09-30T06:09:15Z 2024-09-30T06:09:15Z 2024-08-20 Lenvatinib; Pembrolizumab; Metastatic colorectal cancer Lenvatinib; Pembrolizumab; Cáncer colorrectal metastásico Lenvatinib; Pembrolizumab; Càncer colorectal metastàtic Purpose Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC. Methods In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator's choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov (NCT04776148), and has completed recruitment. Results Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm. Conclusion In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed. Roche (Inst), Bristol Myers Squibb (Inst), SERVIER (Inst), Amgen (Inst), Array BioPharma (Inst), MedImmune (Inst), Pierre Fabre (Inst), Sanofi (Inst), Merck (Inst), BeiGene (Inst), Celgene (Inst), Debiopharm Group (Inst), Genentech (Inst), HalioDx (Inst), Hutchison MediPharma (Inst), Janssen-Cilag SA (Inst), Menarini (Inst), Merck Sharp&DohmedeEspañaSA(Inst),MerusNV(Inst),MiratiTherapeutics (Inst), Novartis (Inst), Pfizer (Inst), PharmaMar (Inst), Taiho Pharmaceutical (Inst), AstraZeneca (Inst), Boehringer Ingelheim (Inst), AbbVie (Inst), Bayer (Inst), Bioncotech (Inst), BioNTech RNA Pharmaceuticals GMBH (Inst), Biontech Small Molecules GMBH (Inst), Boehringer Ingelheim Spain (Inst), Daiichi Sankyo Inc (Inst), Gercor (Inst), Hoffmann-La-Roche Ltd (Inst), Hutchison MediPharma (Inst), IovanceBiotherapeutics (Inst), JanssenResearch&Development(Inst), Menarini (Inst), Nouscom SRL (Inst), Novartis FarmacÃutica SA (Inst), PledPharma (Inst), Redx Pharma (Inst), Scandion Oncology (Inst), Seagen(Inst), Sotio (Inst), Taiho PharmaUSA(Inst), WntResearch(Inst) http://hdl.handle.net/11351/11981 Anticossos monoclonals - Ús terapèutic Quimioteràpia combinada Recte - Càncer - Tractament Còlon - Càncer - Tractament DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study