Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Mar 1;25(1):382.
doi: 10.1186/s12885-025-13749-1.

Exploring Zanidatamab's efficacy across HER2-positive Malignancies: a narrative review

Warisha Kanwal  1 , Kaneez Narjis  2 , Sarah Musani  3 , Fnu Nancy  4 , Laiba Qureshi  2 , Muhammad Mudasir  5 , Rohma Naseem  6 , Fnu Tooba  7 , Juvairia Yousuf  3 , Kanza Farhan  4 , Hadiya Javed  3 , Mohammed Mahmmoud Fadelallah Eljack  8
Affiliations
Review

Exploring Zanidatamab's efficacy across HER2-positive Malignancies: a narrative review

Warisha Kanwal et al. BMC Cancer. .

Abstract

Background: HER2-positive cancers involve amplification or overexpression of the HER2 gene, leading to aggressive tumor growth across several cancer types, including breast, gastric, ovarian, and pancreatic cancers. Detection methods such as immunohistochemistry, next-generation sequencing, and fluorescence in situ hybridization are used, with new advancements like biosensors and circulating tumor DNA offering improved diagnostic potential. Treatment strategies have evolved, including anti-HER2 drugs like trastuzumab and newer agents like zanidatamab, which show promise against HER2-positive malignancies.

Methods: A comprehensive search of the following academic databases was performed including PubMed, Cochrane Library, and clinicaltrials.gov. A detailed search string was made. Studies were selected based on whether they contained the keywords and if they reported the details of treatment for zanidatamab. A total of 16 studies were selected. Abstracts were independently examined by one author and critically reviewed by another and if there were any conflicting viewpoints they were discussed until consensus was reached.

Discussion: Zanidatamab has shown promising clinical outcomes in several HER2-positive cancers, including biliary tract, breast, gastric, and lung cancers, with high disease control rates and progression-free survival. Although it is not yet FDA-approved, it has received priority review for HER2-positive biliary tract cancer, with an FDA decision expected in November 2024. The safety profile of zanidatamab has been well-studied. The most common side effects include diarrhea, infusion reactions, and other mild to moderate treatment-related adverse events. In combination with Palbociclib for HER2-positive breast cancer, more severe side effects were observed, resulting in some patients discontinuing treatment. However, no treatment-related deaths have been reported across trials. While its anticancer efficacy and manageable safety profile are promising, long-term safety and efficacy data are still needed. Early clinical trials demonstrate strong efficacy, though some side effects, such as diarrhea and decreased ejection fraction, were noted. Future research should focus on understanding potential resistance mechanisms and establishing zanidatamab's broader role in the treatment landscape of HER2-positive cancers.

Conclusion: In summary, zanidatamab has shown significant tumor response, progression-free survival, disease control, and improved quality of life in early trials, however, the lack of long-term safety and efficacy data remains a key limitation, requiring further research.

Keywords: Bispecific antibody; Efficacy; HER2; Malignancies; Outcome; Targeted therapy; Zanidatamab.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mechanism of Action of Zanidatamab
See this image and copyright information in PMC

References

    1. Iqbal N, Iqbal N. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014 Sep 7 [cited 2024 Sep 7]; 2014: 1–9. Available from: https://pubmed.ncbi.nlm.nih.gov/25276427/. - PMC - PubMed
    1. Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z, Kurzrock R. HER2 expression status in diverse cancers: review of results from 37,992 patients. Cancer Metastasis Rev. 2015 Mar 1 [cited 2024 Sep 7];34(1):157–64. Available from: https://pubmed.ncbi.nlm.nih.gov/25712293/. - PMC - PubMed
    1. Ayasun R, Ozer M, Sahin I. The Role of HER2 Status in the Biliary Tract Cancers. Cancers (Basel). 2023 May 1 [cited 2024 Sep 7];15(9). Available from: https://pubmed.ncbi.nlm.nih.gov/37174094/. - PMC - PubMed
    1. Li S, Wu J, Huang O, He J, Zhu L, Chen W, et al. HER2 positivity is not associated with adverse prognosis in high-risk estrogen receptor-positive early breast cancer patients treated with chemotherapy and trastuzumab. Breast. 2020 Dec 1 [cited 2024 Sep 7]; 54: 235–41. Available from: https://pubmed.ncbi.nlm.nih.gov/33166784/. - PMC - PubMed
    1. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK. 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, randomized controlled trial. Lancet (London, England). 2010;376(9742):687–97. 10.1016/S0140-6736(10)61121-X. - PubMed

MeSH terms