Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study
Copyright policy )Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III, Randomized LEAP-015 Study
PURPOSE The phase III randomized open-label LEAP-015 study (ClinicalTrials.gov identifier: NCT04662710 ) evaluated first-line lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy for advanced metastatic gastroesophageal adenocarcinoma. METHODS Eligible participants 18 years and older with untreated human epidermal growth factor receptor 2–negative locally advanced unresectable or metastatic gastroesophageal adenocarcinoma were randomly assigned 1:1 to induction with oral lenvatinib 8 mg once daily plus pembrolizumab 400 mg intravenously once every 6 weeks (×2) and investigators’ choice of capecitabine and oxaliplatin once every 3 weeks (×4) or fluorouracil, leucovorin, and oxaliplatin once every 2 weeks (×6) and consolidation with lenvatinib plus pembrolizumab, or chemotherapy. Dual primary end points were progression-free survival (PFS) and overall survival (OS) in participants with PD-L1 combined positive score (CPS) ≥1 and all participants. Secondary end points included objective response rate (ORR) and duration of response. RESULTS Of 880 participants randomly assigned, 443 received lenvatinib plus pembrolizumab and 437 received chemotherapy. The median follow-ups were 32.2 months (range, 19.0-41.7) in participants with PD-L1 CPS ≥1 and 31.8 months (19.0-41.7) in all participants. At interim analysis, PFS was statistically significant with lenvatinib plus pembrolizumab versus chemotherapy in participants with PD-L1 CPS ≥1 (median, 7.3 v 6.9 months; hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.9]; P = .0012) and all participants (median, 7.2 v 7.0 months; HR, 0.78 [95% CI, 0.66 to 0.92]; P = .0019). The ORR was 59.5% versus 45.4% in participants with PD-L1 CPS ≥1 and 58.0% versus 43.9% in all participants, P < .0001 for both. At final analysis, OS was not statistically significant in participants with PD-L1 CPS ≥1 (median, 12.6 v 12.9 months; HR, 0.84 [95% CI, 0.71 to 1.00]; P = .0244; P value boundary = .0204). Grade ≥3 drug-related adverse event rates were 65% versus 49%. CONCLUSION Lenvatinib plus pembrolizumab and chemotherapy versus chemotherapy provided a statistically significant improvement in PFS in advanced unresectable or metastatic gastroesophageal carcinoma at interim analysis although the clinical significance of this difference seems to be limited. No significant improvement occurred in OS in participants with PD-L1 CPS ≥1.
- Seoul National University Korea (Republic of)
- Technical University of Munich Germany
- Universidad Francisco Marroquín Guatemala
- Hebron University Palestinian-administered areas
- University of Seoul Korea (Republic of)
Male, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized, Esophageal Neoplasms, Other subheadings::Other subheadings::/therapeutic use, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias gástricas, Leucovorin, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados, THERAPY, DOUBLE-BLIND, Antineoplastic Combined Chemotherapy Protocols, ADVANCED GASTRIC-CANCER, Anticossos monoclonals - Ús terapèutic, LEAP-015 Investigators, ORIGINAL REPORTS, Middle Aged, OPEN-LABEL, Progression-Free Survival, Oxaliplatin, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma, Estómac - Càncer - Tractament, Oncology, Quinolines, Female, Fluorouracil, Life Sciences & Biomedicine, Adult, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, Otros calificadores::Otros calificadores::/uso terapéutico, Adenocarcinoma, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Esophageal Neoplasms, Antibodies, Monoclonal, Humanized, Quimioteràpia combinada, Esòfag - Càncer - Tractament, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias del esófago, Stomach Neoplasms, 3211 Oncology and carcinogenesis, Humans, 1112 Oncology and Carcinogenesis, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma, Oncology & Carcinogenesis, Capecitabine, Aged, Science & Technology, Phenylurea Compounds, 1103 Clinical Sciences, Adenocarcinoma - Tractament, JUNCTION, 1ST-LINE
Male, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized, Esophageal Neoplasms, Other subheadings::Other subheadings::/therapeutic use, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias gástricas, Leucovorin, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados, THERAPY, DOUBLE-BLIND, Antineoplastic Combined Chemotherapy Protocols, ADVANCED GASTRIC-CANCER, Anticossos monoclonals - Ús terapèutic, LEAP-015 Investigators, ORIGINAL REPORTS, Middle Aged, OPEN-LABEL, Progression-Free Survival, Oxaliplatin, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma, Estómac - Càncer - Tractament, Oncology, Quinolines, Female, Fluorouracil, Life Sciences & Biomedicine, Adult, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, Otros calificadores::Otros calificadores::/uso terapéutico, Adenocarcinoma, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Esophageal Neoplasms, Antibodies, Monoclonal, Humanized, Quimioteràpia combinada, Esòfag - Càncer - Tractament, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias del esófago, Stomach Neoplasms, 3211 Oncology and carcinogenesis, Humans, 1112 Oncology and Carcinogenesis, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma, Oncology & Carcinogenesis, Capecitabine, Aged, Science & Technology, Phenylurea Compounds, 1103 Clinical Sciences, Adenocarcinoma - Tractament, JUNCTION, 1ST-LINE
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