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

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.

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.

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.

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.