Ado-trastuzumab Emtansine in HER2-Overexpressing Metastatic NSCLC
In patients with previously treated HER2-overexpressing metastatic non–small cell lung cancer (NSCLC), treatment with ado-trastuzumab emtansine (formerly known as T-DM1) led to objective responses only among those with the strongest overexpression of HER2. These primary results from an ongoing phase II trial (ClinicalTrials.gov identifier NCT02289833) were presented by Thomas Stinchcombe, MD, of Duke University, at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8509).
Ado-trastuzumab emtansine is approved for the treatment of HER2-positive metastatic breast cancer, but this is reportedly the first study to detail the clinical activity of this agent in HER2-overexpressing metastatic NSCLC.
Of the 393 patients screened for the study, 102 (27%) were IHC2+ (immunohistochemistry 2+ [≥ 10% cells stained with 2+ intensity]) and 29 (7%) were IHC3+ (immunohistochemistry 3+ [≥ 10% cells stained with 3+ intensity]). In total, 49 patients (29 IHC2+ and 20 IHC3+) received ado-trastuzumab emtansine at the standard dose of 3.6 mg/kg every 3 weeks.
After a median follow-up of 16 months, the overall response rate was 0% among patients testing IHC2+. However, partial responses (20%) were observed among those testing IHC3+, with a median duration of response of 7.3 months.
It can be especially challenging to select the patients in this subset most likely to benefit from HER2-targeted therapy, the investigators reported, so additional molecular analyses to refine markers are currently underway.