Study Identifies Subset of Patients With Lung Adenocarcinoma Who Have HER2 Alterations

Researchers have found that about 6% of patients with non–small cell lung cancer (NSCLC) and KRAS, EGFR, or ALK gene mutations may also have HER2 alterations, according to recent findings presented by Dahake et al at the 2024 ASCO Annual Meeting (Abstract 8534).  

Background

Lung adenocarcinoma is a type of NSCLC that originates in the glands lining the organs. When altered, the HER2 protein—which is involved in normal cell growth—can be produced in larger amounts and ultimately lead to the development of certain types of cancers. HER2 mutations are commonly found in patients with lung adenocarcinoma who have little to no history of smoking. 

“Mutations in the … HER2 and ERBB2 [genes] are oncogenic in lung adenocarcinoma. The purpose of this study was to investigate and characterize HER2 alterations along with [their] association with other driver genes. With a more comprehensive understanding of the HER2 genomic landscape, we hope to guide further therapeutic developments,” emphasized lead study author Nikita Dahake, MD, a second year internal medicine resident at Temple University Hospital.

This study is particularly relevant given the fact that recently, the U.S. Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki as a secondary treatment option in patients with HER2-mutated NSCLC.

Study Methods and Results

In this study, the researchers used existing genomic data to analyze the association between HER2 alterations and mutations in other driver genes. They detailed that in their research, alterations referred to either gene mutations or amplifications. The researchers then classified patients with lung adenocarcinoma as having KRAS-mutated, EGFR-mutated, or EML4–ALK fusion–mutated NSCLC. The remaining patients were classified as KRAS/EGFR/ALK other.

The researchers discovered a significant rate of co-occurring HER2 mutations and amplifications in patients with lung adenocarcinoma. Although HER2 could be found in 1% to 4% of patients with NSCLC, both HER2 mutations and amplifications could be identified in up to 6% of patients in the KRAS/EGFR/ALK other cohort.

Further, based on a limited number of patients, those with high HER2 expression without a history of smoking were potentially more likely to experience worse median overall survival.

Conclusions

“Future research endeavors focused on studying long-term clinical outcomes in patients with HER2 [mutations], comutations, and prior therapies will be crucial and informative,” concluded Dr. Dahake.

Disclosure: For full disclosures of the study authors, visit meetings.asco.org.