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HER-2 mutation found in advanced lung cancer
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Nearly 3% of patients with advanced lung adenocarcinoma tested positive for the HER-2 gene, the common driver mutation for breast cancer, according to an analysis of The Lung Cancer Mutation Consortium.
Thus, HER-2-targeted therapies should be investigated for this patient population, according to the researchers.
“In this study, outcomes for HER-2-positive lung cancer patients treated with conventional therapies were similar to outcomes for HER-2-negative patients treated in the same way,” Paul A. Bunn Jr., MD, professor of lung cancer at University of Colorado School of Medicine, said in a press release. “But the question remains: What would the outcomes have been for these patients if they had gotten HER-2-directed therapy?”
The HER-2 gene is amplified in around 15% to 20% of patients with breast cancer and is associated with poorer outcomes.
Researchers also have found that the HER-2 protein is overexpressed in 6% to 30% of patients with lung cancer, and gene amplification occurs in 2% to 20%. Reports have shown that HER-2-mutations occur exclusively in patients with adenocarcinoma, and more commonly in women and never-smokers.
Fourteen U.S. academic centers collaborated to establish the Lung Cancer Mutation Consortium to determine the prevalence, clinical features and outcomes associated with 10 oncogenic drivers in patients with lung adenocarcinomas.
In this analysis, Bunn Jr. and colleagues used consortium data to report the prevalence of HER-2 and how its presence can help guide therapeutic decisions using targeted therapies. This is the first analysis of HER-2 mutations in lung cancer that is limited to patients with advanced disease and that described treatment and survival outcomes.
Of 1,007 patients in the consortium with adequate tumor tissue, 920 underwent testing for HER-2 mutations. Twenty-four patients (2.6%; 95% CI, 2-4; median age, 62 years) harbored exon 20 insertion mutations at codon 775. One patient had a concurrent MET factor amplification.
Most of the patients with a HER-2 mutation were women (58%), never- (71%) or former smokers (25%), and had advanced disease (80%).
Twelve patients (50%) with a HER-2 mutation received HER-2-targeted therapy. Median survival was 2.09 years for these patients compared with 1.37 years for patients who did not receive targeted therapy.
“These treatments seem to have activity, but there just aren't enough patients to know for sure whether HER-2-directed therapy is better than giving chemotherapy, or if one HER-2 treatment is better than another,” Bunn said.
In comparison, among the rest of the consortium, median survival was 2.62 years for patients with wild-type HER-2, 3.5 years for those who received therapy directed at other targets, and 2.4 years for those who did not receive targeted therapy.
Previous research showed EGFR inhibitors gefitinib (Iressa, AstraZeneca) and erlotinib (Tarceva; Genentech, Astellas) are effective in lung cancers that overexpress EGFR and HER-2. This could suggest a potential role for HER-2 inhibition in HER-2-positive cancers, according to the release.
“Sometimes the criteria for HER-2 positivity is a high level of HER-2 protein, sometimes it's overexpression of the HER-2 gene and sometimes it's high HER-2 copy number,” Bunn said. “We don't know if some HER-2 drugs work better than others in these settings.”
Clinical trials of certain HER-2 inhibitors and antibody-drug conjugates targeting HER-2 are ongoing.
“We believe the further development of therapies that more effectively target HER-2 mutations still has the potential to improve outcomes for this group of patients with a poor prognosis,” the researchers wrote. – by Melinda Stevens
Disclosures: Bunn Jr. reports he has no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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