Education, Science, Technology, Innovation and Life
Open Access
Sign In
  1. Home
  2. Journals
  3. MEDS Clinical Medicine
  4. Vol 5, Issue 4, 2024

Meta-Analysis of the Efficacy and Safety of HER2-ADC in the Treatment of Advanced Gastric Cancer

Download as PDF

DOI: 10.23977/medsc.2024.050419 | Downloads: 12 | Views: 672

Author(s)

Wang Xun 1, Yuhong Xu 1

Affiliation(s)

1 College of Pharmacy, Dali University, Dali, Yunnan, China

Corresponding Author

Yuhong Xu

ABSTRACT

This meta-analysis aims to assess the efficacy and safety of HER2-targeted antibody-drug conjugates (ADCs) in patients with advanced gastric cancer (AGC), providing evidence-based references for the clinical utilization and safety evaluation of HER2-targeted ADCs. Comprehensive search was performed across multiple Chinese and English databases, including Embase, PubMed, Cochrane Library, Web of Science, WanFang, CNKI, VIP, as well as abstracts from major international conferences, up to February 20, 2023. Meta-analysis was conducted using STATA12 software, with pooled rates, means, and 95% confidence intervals (CIs) used to summarize the efficacy and safety of HER2-targeted ADCs in AGC treatment. A Seven studies, involving a total of 671 AGC patients treated with HER2-targeted ADCs, were included. The pooled objective response rate (ORR) of HER2-targeted ADCs was 31.3% (95%CI: 21.4%-41.2%), with a disease control rate (DCR) of 72.5% (95%CI: 57.8%-87.1%). The median overall survival (OS) was 9.91 months (95%CI: 7.71-12.21 months), and the median progression-free survival (PFS) was 4.20 months (95%CI: 3.28-5.11 months). The incidence of any grade adverse events (AEs) was 99.8% (95%CI: 98.5%-100.0%), while the incidence of grade 3 or higher AEs was 59.1% (95%CI: 43.7%-74.6%). The most frequent grade 3 or higher AEs were anemia (22.2%, 95%CI: 19.1%-25.5%) and interstitial pneumonia (1.9%, 95%CI: 1.0%-3.3%). The incidence of serious adverse events (SAEs) was 30.3% (95%CI: 20.2%-40.4%). Sensitivity analysis showed robust findings with a low risk of publication bias.HER2-targeted ADCs demonstrate moderate efficacy in AGC treatment, with a generally manageable safety profile.

KEYWORDS

HER2; antibody-drug conjugates; advanced gastric cancer; efficacy; safety; meta-analysis

CITE THIS PAPER

Wang Xun, Yuhong Xu, Meta-Analysis of the Efficacy and Safety of HER2-ADC in the Treatment of Advanced Gastric Cancer. MEDS Clinical Medicine (2024) Vol. 5: 141-152. DOI: http://dx.doi.org/10.23977/medsc.2024.050419.

REFERENCES

[1] SUNG H F J, SIEGEL R L, ET AL. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer Statistics, 2021 [J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[3] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[4] WANG S E, NARASANNA A, PEREZ-TORRES M, et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors [J]. Cancer Cell, 2006, 10(1): 25-38.
[5] Yarden Y. Biology of HER2 and its importance in breast cancer. [J]. Oncology, 2001, 61 Suppl 2: 1-13.
[6] L D READ D K J, D J SLAMON, B S KATZENELLENBOGEN. Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines [J]. Cancer Res, 1990, 50(13): 3947-3951.
[7] Sliwkowski M X. Ready to partner [J]. Nat Struct Biol, 2003, 10(3): 158-159.
[8] NIAZI S, PUROHIT M, SONAWANI A, et al. Revealing the molecular interactions of aptamers that specifically bind to the extracellular domain of HER2 cancer biomarker protein: An in silico assessment [J]. J Mol Graph Model, 2018, 83: 112-121.
[9] GRAVALOS C, JIMENO A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target [J]. Ann Oncol, 2008, 19(9): 1523-1529.
[10] BARTLEY A N, WASHINGTON M K, VENTURA C B, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology [J]. Am J Clin Pathol, 2016, 146(6): 647-669.
[11] THUSS-PATIENCE P C, SHAH M A, OHTSU A, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study [J]. Lancet Oncol, 2017, 18(5): 640-653.
[12] JANJIGIAN Y Y, KAWAZOE A, YANEZ P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer [J]. Nature, 2021, 600(7890): 727-730.
[13] KANG Y K, CHEN L T, RYU M H, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial [J]. Lancet Oncol, 2022, 23(2): 234-247.
[14] WANG F H, ZHANG X T, LI Y F, et al. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2021 [J]. Cancer Commun (Lond), 2021, 41(8): 747-795.
[15] M T. Handbook for Systematic Reviews of Interventions. Journal of Multidisciplinary Evaluation [J]. Handbook for Systematic Reviews of Interventions Journal of Multidisciplinary Evaluation, 2008, 6:142-148.
[16] SLIM K N E, KWIATKOWSKI F, PANIS Y. Methodological index for non-randomized studies (minors): development and validation of a new instrument [J]. Anz Journal of Surgery, 2015, 73:712-716.
[17] HIGGINS JP T S, DEEKS JJ, ALTMAN DG. Measuring inconsistency in meta-analyses [J]. BMJ (Clinical research ed), 2003, 327:557-560.
[18] EGGER M D S G, SCHNEIDER M, MINDER C. Bias in meta-analysis detected by a simple, graphical test [J]. BMJ, 1997, 315:629-634.
[19] SHITARA K, IWATA H, TAKAHASHI S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study [J]. Lancet Oncol, 2019, 20(6): 827-836.
[20] SHITARA K, BANG Y J, IWASA S, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer [J]. N Engl J Med, 2020, 382(25): 2419-2430.
[21] ZHANG Y, QIU M Z, WANG J F, et al. Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma [J]. Cell Rep Med, 2022, 3(11): 100814.
[22] YAMAGUCHI K, BANG, Y. J., IWASA, S., SUGIMOTO, N., RYU, M. H., SAKAI, D., CHUNG, H. C., KAWAKAMI, H., YABUSAKI, H., LEE, J., SHIMOYAMA, T., LEE, K. W., SAITO, K., KAWAGUCHI, Y., KAMIO, T., KOJIMA, A., SUGIHARA, M., & SHITARA, K. Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial [J]. Journal of clinical oncology, 2023, 41(4): 816-825.
[23] PENG Z, LIU T, WEI J, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study [J]. Cancer Commun (Lond), 2021, 41(11): 1173-1182.
[24] VAN CUTSEM E, DI BARTOLOMEO M, SMYTH E, et al. LBA55 Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen [J]. Annals of Oncology, 2021, 32.
[25] BANG Y J, VAN CUTSEM E, FEYEREISLOVA A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial [J]. Lancet, 2010, 376(9742): 687-697.
[26] SMYTH E C, NILSSON M, GRABSCH H I, et al. Gastric cancer [J]. Lancet, 2020, 396(10251): 635-648.
[27] LIN S J, GAGNON-BARTSCH J A, TAN I B, et al. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas [J]. Gut, 2015, 64(11): 1721-1731. 
[28] CANCER GENOME ATLAS RESEARCH N. Comprehensive molecular characterization of gastric adenocarcinoma [J]. Nature, 2014, 513(7517): 202-209.

Subscription
E-Mail Alert
Most popular papers
Call for Special Issue
Publication Ethics & OA Statement
Plagiarism Policy
Contact Us
Downloads: 9214
Visits: 556152

Sponsors, Associates, and Links

All published work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2016 - 2031 Clausius Scientific Press Inc. All Rights Reserved.