دورية أكاديمية
HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial
| العنوان: | HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial |
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| المؤلفون: | Corso, Simona, Raimondi, Alessandra, Berrino, Enrico, Tabernero Caturla, Josep, Pietrantonio, Filippo, Bellomo, Sara Erika, Manca, Paolo |
| المساهمون: | Institut Català de la Salut, Pietrantonio F, Manca P, Raimondi A Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Bellomo SE, Corso S Department of Oncology, University of Turin, Turin, Italy. Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Berrino E Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Department of Medical Sciences, University of Turin, Turin, Italy. Tabernero J Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Uvic-UCC, IOB-Quiron, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | American Association for Cancer Research |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Estómac - Càncer - Tractament, Medicaments antineoplàstics - Ús terapèutic, Estómac - Càncer - Aspectes genètics, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach 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, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias gástricas, 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 |
| الوصف: | Resistance mechanisms; Advanced gastric cancer; Trastuzumab ; Mecanismos de resistencia; Cáncer gástrico avanzado; Trastuzumab ; Mecanismes de resistència; Càncer gàstric avançat; Trastuzumab ; Purpose: In JACOB trial, pertuzumab added to trastuzumab-chemotherapy did not significantly improve survival of patients with HER2-positive metastatic gastric cancer, despite 3.3 months increase versus placebo. HER2 copy-number variation (CNV) and AMNESIA panel encompassing primary resistance alterations (KRAS/PIK3CA/MET mutations, KRAS/EGFR/MET amplifications) may improve patients’ selection for HER2 inhibition. Experimental Design: In a post hoc analysis of JACOB on 327 samples successfully sequenced by next-generation sequencing (NGS; Oncomine Focus DNA), HER2 CNV, HER2 expression by IHC, and AMNESIA were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) by univariable/multivariable models. Results: Median HER2 CNV was 4.7 (interquartile range, 2.2–16.9). HER2 CNV-high versus low using the median as cutoff was associated with longer median PFS (10.5 vs. 6.4 months; HR = 0.48; 95% confidence interval: 0.38–0.62; P < 0.001) and OS (20.3 vs. 13.0 months; HR = 0.54; 0.42–0.72; P < 0.001). Combining HER2 CNV and IHC improved discriminative ability, with better outcomes restricted to HER2-high/HER2 3+ subgroup. AMNESIA positivity was found in 51 (16%), with unadjusted HR = 1.35 (0.98–1.86) for PFS; 1.43 (1.00–2.03) for OS. In multivariable models, only HER2 CNV status remained significant for PFS (P < 0.001) and OS (P = 0.004). Higher ORR was significantly associated with IHC 3+ [61% vs. 34% in 2+; OR = 3.11 (1.89–5.17)] and HER2-high [59% vs. 43% in HER2-low; OR = 1.84 (1.16–2.94)], with highest OR in the top CNV quartile. These biomarkers were not associated with treatment effect of pertuzumab. Conclusions: HER2 CNV-high assessed by NGS may be associated with better ORR, PFS, and OS in a JACOB subgroup, especially if combined with HER2 3+. The negative ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1557-3265 |
| العلاقة: | Clinical Cancer Research;29(3); https://doi.org/10.1158/1078-0432.CCR-22-2533Test; Pietrantonio F, Manca P, Bellomo SE, Corso S, Raimondi A, Berrino E, et al. HER2 copy number and resistance mechanisms in patients with HER2-positive advanced gastric cancer receiving initial trastuzumab-based therapy in JACOB trial. Clin Cancer Res. 2023 Feb 1;29(3):571–80.; https://hdl.handle.net/11351/9411Test; 000928165300001 |
| DOI: | 10.1158/1078-0432.CCR-22-2533 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.CCR-22-2533Test https://hdl.handle.net/11351/9411Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7B115DED |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15573265 |
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| DOI: | 10.1158/1078-0432.CCR-22-2533 |