Efficacy and safety of trastuzumab deruxtecan in HER2-positive advanced gastric and gastroesophageal junction cancers: A meta-analysis of real-world studies and clinical trials.
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Le résumé fourni par la source
402 Background: Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody-drug conjugate (ADC) with a cytotoxic payload. TDXd was approved in 2021 to be used in advanced gastric or GEJ cancers. Although given the recent approval, real-world evidence on efficacy and safety is limited. We sought to evaluate the efficacy and safety of T-DXd through a combined meta-analysis of clinical trials and real-world studies. Methods: A comprehensive search was conducted across PubMed, Embase, Scopus, and Clinicaltrials.gov databases. The original studies evaluating T-DXd in patients with metastatic/recurrent gastric/gastroesophageal junction (GEJ) cancers were included in the analysis. The pooled objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events (AEs) were analyzed. A random-effects model was used for meta-analysis, and the heterogeneity of the data was evaluated by Chi-sq Q test and the I 2 statistic using OpenMeta [Analyst] (Tufts Medical Center, Boston, MA, USA). Results: This meta-analysis incorporated 8 studies (3 phase II clinical trials, 5 retrospective studies) comprising 915 patients with advanced HER2-positive gastric/GEJ cancer. The median patient age was 66.5 years (range: 27–89), with 75.4% males, 70.4% Asian, and 29.0% Caucasians. 77.9% had an ECOG performance status of 0–1, while 21.8% had ECOG ≥2. Histologically, 53.6% had intestinal and 22.9% diffuse-type adenocarcinoma. HER2 overexpression (IHC3+) was observed in 75.8% of evaluable cases, and 22.4% were IHC2+/FISH positive. 77.6% had primary gastric and 22.4% GEJ tumors. The median line of therapy was 3 (range: 2–11), with prior immune checkpoint inhibitor use in 31.8% and prior surgery in 44.5% .The pooled ORR was 47.7% (95% CI 43.0-52.4%) and DCR was 82.50% (79.40%–85.72%); PFS and OS were 4.92 and 9.86 months, respectively. Safety analysis revealed grade ≥3 AEs in 48.2% of patients, neutropenia (24.5%) being the most common. Treatment discontinuation due to adverse events occurred in 12.2%, and dose reductions were required in 21.5%. Patient-reported outcomes were not assessed in any of the studies. Conclusions: Our meta-analysis, encompassing both clinical trials and real-world data, confirms the encouraging efficacy of T-DXd in gastric/GEJ cancers, with a pooled ORR of 47.7% and a median PFS of 4.92 months, and supports its use as an early-line treatment in this challenging disease landscape. This analysis also highlights the significant incidence of grade ≥3 AEs, particularly neutropenia, which necessitates vigilant monitoring and proactive management. Future research should focus on optimizing patient selection, exploring combination therapies, and refining dosing strategies to maximize clinical benefit while mitigating toxicity.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Efficacy and safety of trastuzumab deruxtecan in HER2-positive advanced gastric and gastroesophageal junction cancers: A meta-analysis of real-world studies and clinical trials.
- Date Crossref
- 10/01/2026
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Jacksonville College pays non établi dans la noticeUniversité ou école supérieure
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WinnMed pays non établi dans la noticeOrganisation à but non lucratif
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Mayo Clinic in Florida pays non établi dans la noticeÉtablissement de santé
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Karachi Medical and Dental College pays non établi dans la noticeUniversité ou école supérieure
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Anne Arundel Medical Center Department of Internal Medicine pays non établi dans la noticeÉtablissement de santé
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The University of Texas MD Anderson Cancer Center pays non établi dans la noticeÉtablissement de santé
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Thomas Jefferson University Sidney Kimmel Comprehensive Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
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George Washington University Hospital pays non établi dans la noticeÉtablissement de santé
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University of Vermont Medical Center pays non établi dans la noticeÉtablissement de santé
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Mayo Clinic Florida pays non établi dans la noticeÉtablissement de santé
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Corewell Health William Beaumont University Hospital pays non établi dans la noticeUniversité ou école supérieure
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The University of Texas School of Public Health pays non établi dans la noticeUniversité ou école supérieure
Jacksonville College, WinnMed et Mayo Clinic in Florida, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.