Temple University Hospital and Fox Chase Cancer Center Researchers Characterize HER2 Mutations in Patients With Lung Adenocarcinoma

Human epidermal growth factor 2 (HER2) mutations can be identified in up to 6% of non-small cell lung cancer cases where KRAS, EGFR, or ALK gene mutations are also found, according to the results of research from Temple University Hospital and Fox Chase Cancer Center presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Mutations in the human epidermal growth receptor 2, such as HER2 and ERBB2, are oncogenic in lung adenocarcinoma. The purpose of this study was to investigate and characterize HER2 alterations along with its association with other driver genes. With a more comprehensive understanding of the HER2 genomic landscape, we hope to guide further therapeutic developments,” said Nikita Dahake, MD, a second year internal medicine resident at Temple University Hospital. 

Adenocarcinoma is a type of non-small cell lung cancer that develops in the glands lining the organs. HER2 is a protein involved in normal cell growth that, when altered, can be produced in larger amounts and ultimately lead to certain types of cancers. HER2 mutations are commonly found in adenocarcinoma non-small cell lung cancer patients with little to no smoking history.

This study is particularly relevant given the recent Food and Drug Administration approval of the drug trastuzumab deruxtecan, which is also known by the brand name Enhertu, as a secondary treatment for patients with HER2-mutated non-small cell lung cancer.

Researchers used existing genomic data to analyze how HER2 alterations are associated with alterations in other driver genes. In this case, alterations can refer to either gene mutation or amplification, which is an increase in the number of copies of a gene, a phenomenon that is common in cancer cells and can cause them to grow or become resistant to drugs.

In the study, lung adenocarcinoma patients were classified as having KRAS-mutated, EGFR-mutated, or EML4-ALK fusion-mutated non-small cell lung cancer. The remainder were classified as KRAS/EGFR/ALK other (KEAother).

In contrast to prior reports, there was a significant rate of co-occurring HER2 mutations and HER2 amplification in cases of lung adenocarcinoma. Researchers found that while HER2 can be identified in 1% to 4% of patients with non-small cell lung cancer, both HER2 mutations and amplifications could be found in up to 6% of cases in the KEAother cohort.

Additionally, the study found that based on a limited number of patients, those with high HER2 expression who never smoked trended toward worse median overall survival.

“Future research endeavors focused on studying long-term clinical outcomes in patients with HER2 gene alterations, co-mutations, and prior therapies will be crucial and informative,” said Dahake.

“As an aspiring oncologist, I am thrilled and honored to present our team’s work at ASCO. I am eager to connect with oncology professionals from around the word and learn about groundbreaking science to help transform cancer-directed care.”

The study, “Characterization of HER2 Alterations in Lung Adenocarcinoma,” was presented in a poster session at the ASCO meeting, which is being held May 31-June 4 in Chicago.