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The Potential of HER2-Targeted Therapies in Gastroesophageal Adenocarcinoma

Jazz is redefining what is possible in the treatment of cancer by improving standards of care across the oncology spectrum with life-saving or life-extending therapies. As we advance our work and capabilities in oncology, we continue to focus on people for whom we can have the greatest impact.

One of the greatest areas of need we hope to positively impact is the understanding and treatment of gastroesophageal adenocarcinoma (GEA). GEA includes stomach cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. It is the fifth most frequent tumor and the third leading cause of cancer-related deaths worldwide.i

Despite the prevalence of GEA, the complex nature of these cancers has led to challenges in developing treatment options. As such, the overall prognosis for patients with GEA remains poor, with a global 5-year survival rate of less than 30 percent for gastric cancer and about 19 percent for GEA.ii To potentially help improve survival, one area we’re exploring is HER2-targeted therapies. HER2 is a protein that can overexpress in certain tumor types, including GEA, and cause cancers to grow at a faster rate.

The Significance of HER2 in GEA and the Role of HER2-Targeted Therapies

The HER2 protein is found in all cells and plays an important role in cell growth and survival.iii When cancer cells develop with higher-than-normal levels of HER2, they are called HER2-positive. HER2-positive cancers tend to grow and spread faster than cancers that are HER2-negative, which can impact quality of life and lead to a higher likelihood of death.iii

Anti-HER2 medicines, commonly referred to as “HER2-targeted therapies,” work in a variety of ways. Some HER2-targeted therapies target HER2 receptor expression or interfere with HER2 pathway activation, while others work by blocking the HER2 receptors from receiving the growth signals in HER2-positive cancer cells, and in doing so, can slow or stop the growth of HER2-postive cancers.iii

Understanding the role of HER2 and the level of HER2-expression in cancers like GEA is a key component in improving therapy options for patients with this type of cancer, as approximately 20% of people with GEA have HER2-positivity.iv,v,vi Given that HER2 has emerged as a well-validated target for patients whose cancer displays HER2-positivity, testing for HER2-expression in patients diagnosed with GEA is critical to determining the appropriate treatment option.

Looking Ahead to the Future

As our pipeline continues to expand into new areas of development in difficult-to-treat cancers, we are focused on innovative research, including targeted therapy. Investigating our HER2-targeted bispecific antibody – which has biparatopic binding to two, non-overlapping HER2 epitopes – is a prime example of our innovative research in action, and we look forward to continuing to explore the potential of this therapy not just in GEA but across tumor types.

References

iGambardella V, Fleitas T, Tarazona N, Papaccio F, Huerta M, Roselló S, Gimeno-Valiente F, Roda D, Cervantes A. Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress. J Clin Med. 2020 Sep 22;9(9):3049. doi: 10.3390/jcm9093049. PMID: 32971757; PMCID: PMC7564841.       
iiBattaglin F, et al. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell International. 2018;18(99).     
iiiIqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;2014:852748.       
ivAbrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.       
vVan Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.       
viStroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249.