Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial

Abstract

<div class="section"> <a class="named-anchor" id="d3393440e324"> <!-- named anchor --> </a> <h5 class="section-title" id="d3393440e325">Purpose</h5> <p id="d3393440e327">Human epidermal growth factor receptor 2 ( <i>HER2</i>, <i>ERBB2</i>)–activating mutations occur in 2% of lung cancers. We assessed the activity of ado-trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, in a cohort of patients with <i>HER2</i>-mutant lung cancers as part of a phase II basket trial. </p> </div><div class="section"> <a class="named-anchor" id="d3393440e338"> <!-- named anchor --> </a> <h5 class="section-title" id="d3393440e339">Patients and Methods</h5> <p id="d3393440e341">Patients received ado-trastuzumab emtansine at 3.6 mg/kg intravenously every 3 weeks until progression. The primary end point was overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A Simon two-stage optimal design was used. Other end points included progression-free survival and toxicity. HER2 testing was performed on tumor tissue by next generation sequencing, fluorescence in situ hybridization, immunohistochemistry, and protein mass spectrometry. </p> </div><div class="section"> <a class="named-anchor" id="d3393440e343"> <!-- named anchor --> </a> <h5 class="section-title" id="d3393440e344">Results</h5> <p id="d3393440e346">We treated 18 patients with advanced <i>HER2</i>-mutant lung adenocarcinomas. The median number of prior systemic therapies was two (range, zero to four prior therapies). The partial response rate was 44% (95% CI, 22% to 69%), meeting the primary end point. Responses were seen in patients with <i>HER2</i> exon 20 insertions and point mutations in the kinase, transmembrane, and extracellular domains. Concurrent <i>HER2</i> amplification was observed in two patients. HER2 immunohistochemistry ranged from 0 to 2+ and did not predict response, and responders had low HER2 protein expression measured by mass spectrometry. The median progression-free survival was 5 months (95% CI, 3 to 9 months). Toxicities included grade 1 or 2 infusion reactions, thrombocytopenia, and elevated hepatic transaminases. No patient stopped therapy as a result of toxicity or died on study. </p> </div><div class="section"> <a class="named-anchor" id="d3393440e357"> <!-- named anchor --> </a> <h5 class="section-title" id="d3393440e358">Conclusion</h5> <p id="d3393440e360">Ado-trastuzumab emtansine is an active agent in patients with <i>HER2</i>-mutant lung cancers. This is the first positive trial in this molecular subset of lung cancers. Further use and study of this agent are warranted. </p> </div>