ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
HER2 Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.Nature communications · 2024Trial
- Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.Targeted oncology · 2026Article
- Advancements in targeted therapy for gastric cancer.Therapeutic advances in gastroenterology · 2026Review
- Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Review
- Article
- Integrating genomic mutations and tumor-infiltrating lymphocytes improves prediction of response to trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Cadonilimab combined with trastuzumab and chemotherapy for HER2-positive gastric cancer with bone marrow metastasis and DIC: a case report and literature review.Frontiers in immunology · 2025Review
- Advances in the treatment of human epidermal growth factor receptor 2-positive gastric cancer.International journal of clinical oncology · 2024Review
- Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Emerging Therapeutic Targets and Future Directions in Advanced Gastric Cancer: A Comprehensive Review.Cancers · 2024Review
- Clinical application of targeted tumour sequencing tests for detecting ERBB2 amplification and optimizing anti-HER2 therapy in gastric cancer.BMC cancer · 2024Article
- Characterization of MET Alterations in 37 Gastroesophageal Cancer Cell Lines for MET-Targeted Therapy.International journal of molecular sciences · 2024Article
- Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A unified DNA- and RNA-based NGS strategy for the analysis of multiple types of variants at the dual nucleic acid level in solid tumors.Journal of clinical laboratory analysis · 2023Article
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn 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
designIn 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.
resultsMedian 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.
conclusionsHER2 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 prognostic role of AMNESIA requires further clinical validation.
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