Study Finds HER2 Mutations in 3% of Lung Cancers

Key Points

  • 71% of patients with a HER2 mutation were never-smokers, with a median age of 62.
  • Median survival for patients receiving HER2-directed therapy was 2.1 years, compared with median survival of 1.4 years for those who did not receive HER2-directed therapy.

The Lung Cancer Mutation Consortium at the University of Colorado Cancer Center reported that 24 of 920 patients (3%) with advanced-stage lung cancer in a recent study had mutations in the gene HER2. According to the study, published by Pillai et al in Cancer, 71% of these patients were never-smokers, with a median age of 62.

The gene HER2 has been known as a breast cancer driver, with therapies approved to target HER2 mutations in this setting. Now, ongoing clinical trials are evaluating the use of HER2-directed therapy against lung cancer testing positive for the mutation. By identifying a significant population of HER2-positive lung cancer patients, the current study demonstrates the need for these therapies.

“In this study, outcomes for HER2-positive lung cancer patients treated with conventional therapies were similar to outcomes for HER2-negative patients treated in the same way. But the question remains: what would the outcomes have been for these patients if they had gotten HER2-directed therapy?” asked Paul Bunn, Jr, MD, FASCO, Distinguished Professor at the University of Colorado Cancer Center and James Dudley Professor of Lung Cancer Research at the University of Colorado School of Medicine.

More Findings From the Study

Of the 24 patients identified with HER2 mutation, 12 received HER2-directed therapy and 12 received conventional therapies (eg, chemotherapy). Median survival for patients receiving HER2-directed therapy was 2.1 years, compared with median survival of 1.4 years for those who did not receive HER2-directed therapy.

“These treatments seem to have activity, but there just aren’t enough patients to know for sure whether HER2-directed therapy is better than giving chemotherapy, or if one HER2 treatment is better than another,” Dr. Bunn explained.

The gene HER2 is closely related to known lung cancer driver EGFR. Both genes code for proteins that function as growth factor receptors. Researchers and physicians have shown success treating EGFR-positive lung cancer, such as EGFR inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Previous work published by Hirsch et al in Oncogene shows these drugs are especially useful against lung cancers that overexpress both EGFR and HER2, implying that in addition to targeting HER2-positive lung cancers with drugs approved to treat HER2-positive breast cancers, there may be a role for HER2 inhibitors in HER2-associated cancers—perhaps both breast and lung.

The use of HER2 drugs may also need to be refined based on the criteria used to define HER2 dependence.

“Sometimes the criteria for HER2 positivity is a high level of HER2 protein, sometimes it’s overexpression of the HER2 gene, and sometimes it’s high HER2 copy number. We don’t know if some HER2 drugs work better than others in these settings,” Dr. Bunn said.

Ongoing clinical trials hope to answer many of these outstanding questions. For example, the HER2 inhibitors neratinib (Nerlynx) and pyrotinib, the monoclonal antibody trastuzumab (Herceptin), and antibody-drug conjugates aimed at HER2 are currently in clinical trials. For now, the current study shows that a significant population of lung cancer patients with HER2 mutations exists. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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