Ado-Trastuzumab Emtansine Achieves Responses in ERBB2-Mutant Lung Cancer

Activating mutations in ERBB2 (also known as HER2) occur in 2% of patients with lung cancer, and no targeted therapies are approved for this patient population. In clinical trials the ERBB2 inhibitor trastuzumab had limited activity in patients with lung cancer selected by ERBB2 protein expression, but Li and colleagues hypothesized that it might produce antitumor responses in patients with ERBB2-mutant lung cancer. Thus, a phase II basket trial evaluating the ERBB2-targeted antibody–drug conjugate ado-trastuzumab emtansine, which links trastuzumab to the antimicrotubule agent emtansine, enrolled a cohort of patients with ERBB2-mutant lung cancer. Ado-trastuzumab emtansine had previously been approved for treatment of patients with ERBB2-amplified or ERBB2-overexpressing metastatic breast cancer. In this basket trial, 18 patients with advanced ERBB2-mutant lung adenocarcinoma were treated with ado-trastuzumab emtansine. Most patients were heavily pretreated with a median of two prior lines of systemic therapy. The primary endpoint was overall response rate, and other endpoints included progression-free survival and toxicity. The overall response rate was 44%, with partial responses achieved in 8 of 18 patients, and the median progression-free survival was 5 months. Responses were seen across ERBB2 mutation subtypes including exon 20 insertions and transmembrane and extracellular domain point mutations, and two patients also had concurrent ERBB2 amplification. Further, responses occurred even in patients with low levels of ERBB2 protein expression. Ado-trastuzumab emtansine was well tolerated, the majority of adverse events were grade 1–2, and there was one incident of grade 3 anemia. There were no dose reductions or treatment discontinuations. Collectively, these findings demonstrate that ado-trastuzumab emtansine has activity against ERBB2-mutant lung cancer, and support its further use and investigation for the treatment of patients with ERBB2-mutant lung cancer.

Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol 2018 Jul 10 [Epub ahead of print].

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