Sistema de Salut de Catalunya
Institut Català de la Salut
[Moehler M] Department of Medicine, University Medical Center of Johannes Gutenberg University, Mainz, Germany. [Oh DY] Department of Hemato Oncology, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. [Kato K] Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. [Arkenau T] Department of Oncology, Sarah Cannon Research, London, UK. [Tabernero J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lee KW] Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Vall d'Hebron Barcelona Hospital Campus
2025-05-02T06:27:04Z
2025-05-02T06:27:04Z
2025-05
Gastric cancer; Gastroesophageal junction cancer; Immunotherapy
Càncer gàstric; Càncer de la unió gastroesofàgica; Immunoteràpia
Cáncer gástrico; Cáncer de la unión gastroesofágica; Inmunoterapia
Introduction Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit–risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%. Methods Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score ≥ 1%. Results At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score ≥ 1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plus ICC [15.0 months (95% confidence interval [CI] 13.3–16.7) vs. 12.8 months (95% CI 12.1–14.1), respectively; stratified hazard ratio 0.77 (95% CI 0.67–0.90)]. Progression-free survival, overall response rate, duration of response, and disease control rate, were also improved. OS improvements were maintained at a 3-year data cutoff (February 28, 2024). Tislelizumab plus ICC had an acceptable safety profile with no new safety signals. Conclusions Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score ≥ 1%. Trial registration number NCT03777657.
This study was funded by BeiGene, Ltd. Rapid service and open access fees are funded by BeiGene, Ltd.
Article
Published version
English
Estómac - Càncer - Tractament; Quimioteràpia combinada; Anticossos monoclonals - Ús terapèutic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized; 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; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados; Otros calificadores::Otros calificadores::/uso terapéutico
Adis
Advances in Therapy;42
https://doi.org/10.1007/s12325-025-03133-7
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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