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Inroads to Targeting HER2-Mutant Lung Cancer Begin Taking Shape

*October 2022*

Targeted treatment options for patients with HER2-mutant non–small cell lung cancer (NSCLC) have been slow to reach benchmarks for approval given the limited patient populations harboring this disease characteristic. Three classes of agents have demonstrated efficacy in patients with HER2-mutant disease: tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and antibody-drug conjugates (ADCs).1 As the pool of available data grows for targeted treatments in this molecular subtype, investigators must stay informed about treatment options to optimize patient care, according to Edward S. Kim, MD, MBA.

“There [are] multiple alterations in HER2 we’ve found over the years,” Kim said in an OncLive® Molecular Targets Workshop. “It’s not just overexpression, we can also have gene amplification mutations. We see this in 1% to 5% of patients with lung cancer and data have showed that this is more frequent in women and never-smokers. We’re seeing more of these EGFR family mutations and most of these HER2 mutations occur in exon 20.”2 Kim is physician in chief at City of Hope Orange County and vice physician in chief at City of Hope National Medical Center, both in California.

Limited progress has been demonstrated with standard NSCLC treatments for patients such as chemotherapy and immunotherapy among patients with HER2-mutant tumors. “Chemotherapy [had] some limited degrees of efficacy [and] immunotherapies have been looked at,” Kim said. “Multiple TKIs have been developed that have a wider range of target nonspecificity.” For example, afatinib (Gilotrif) is approved for patients with NSCLC whose tumors have nonresistant EGFR mutations.3 Despite early efficacy supporting a new drug application for the pan-HER TKI poziotinib for previously treated patients with locally advanced or metastatic NSCLC with HER2 exon 20 insertion mutations, a recent meeting the FDA’s Oncologic Drugs Advisory Committee voted 9-4 that poziotinib’s benefit do not outweigh its risks.4

“We’re seeing some activity with TKIs, especially in the mutation side, but there is also activity with monoclonal antibodies such as trastuzumab [Herceptin] in combinations, and ADCs. They’ve been around for some time; however, they have been accelerating as far as the number of indications and drugs that have been coming to market,” Kim said. Read more.