Li BT, et al. - Experts evaluated the activity of ado-trastuzumab emtansine (a HER2-targeted antibody-drug conjugate) in a cohort of patients with HER2-mutant lung cancers as part of a phase II basket trial. In patients with HER2-mutant lung cancers, ado-trastuzumab emtansine was seen to be an active agent. In this molecular subset of lung cancers, this is the first positive trial.

Methods

• The patients were administered ado-trastuzumab emtansine at 3.6 mg/kg intravenously every 3 weeks until progression.
• Overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was the primary end point.
• Progression-free survival and toxicity were the other end points.
• Authors used a Simon two-stage optimal design.
• They performed HER2 testing on tumor tissue by next generation sequencing, fluorescence in situ hybridization, immunohistochemistry, and protein mass spectrometry.

Results

• There were 18 patients with advanced HER2-mutant lung adenocarcinomas treated.
• As per data, the median number of prior systemic therapies was two (range, zero to four prior therapies).
• Results demonstrated that the partial response rate was 44% (95% CI, 22% to 69%), meeting the primary end point.
• Researchers noted the responses in patients with HER2 exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains.
• They observed concurrent HER2 amplification in two patients.
• The range of HER2 immunohistochemistry was from 0 to 2+ and did not predict response, low HER2 protein expression measured by mass spectrometry was seen in responders.
• Five months was the median progression-free survival (95% CI, 3 to 9 months).
• Grade 1 or 2 infusion reactions, thrombocytopenia, and elevated hepatic transaminases were included in the toxicities.