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Is Ado-Trastuzumab Emtansine Active in HER2-Mutant Lung Cancer?

By: Cordi Craig
Posted: Monday, August 27, 2018

The HER2-targeted antibody-drug conjugate ado-trastuzumab emtansine showed activity in patients with advanced HER2-mutant lung cancers, a new study reported in the Journal of Clinical Oncology. Responses were observed in patients with HER2 exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains.

“This is the first positive trial in this molecular subset of lung cancers,” according to Bob T. Li, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. “Further use and study of this agent are warranted.”

This phase II basket trial evaluated a cohort of 18 patients with stage IV or recurrent HER2-mutant lung cancer. Half of the patients had received prior HER2-targeted therapy. Patients received ado-trastuzumab emtansine until disease progression.

Partial responses were observed in 44% of patients (n = 8), and 39% of patients showed stable disease (n = 7). Of the responders, two were previously untreated and six had received prior lines of therapy, including HER2-targeted treatment with neratinib and trastuzumab. The median progression-free survival was 5 months among all patients and 6 months among responders.

The investigators observed mostly grade 1 or 2 adverse events, including elevated hepatic transaminases (45%), thrombocytopenia (33%), and infusion reactions (28%). Grade 3 anemia occurred in one patient. No treatment-related deaths or grade 4 toxicities were reported.

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