Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety and Biomarkers
Mené sur 49 patients atteints d'un cancer du poumon non à petites cellules surexprimant HER2 et de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du trastuzumab emtansine, un conjugué anticorps-médicament ciblant HER2
Background: HER2-targeted therapy is not standard of care for human epidermal growth factor receptor 2 (HER2)-positive non-small cell lung cancer (NSCLC). This phase II study investigated efficacy and safety of the HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with previously treated advanced HER2-overexpressing NSCLC. Methods: Eligible patients had HER2-overexpressing NSCLC (centrally-tested immunohistochemistry [IHC]), and received previous platinum-based chemotherapy and targeted therapy in the case of EGFR mutation or ALK gene rearrangement. Patients were divided into cohorts based on HER2 IHC (2+, 3+). All patients received T-DM1 3.6 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-determined overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors v1.1. Results: Forty-nine patients received T-DM1 (29 IHC 2+, 20 IHC 3+). No treatment responses were observed in the IHC 2+ cohort. Four partial responses were observed in the IHC 3+ cohort (ORR 20%; 95% confidence interval 5.7-43.7%). Clinical benefit rates were 7% and 30% in the IHC 2+ and 3+ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free and overall survival were similar between cohorts. Three of four responders had HER2 gene amplification. No new safety signals were observed. Discussion : T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3+) advanced NSCLC. Additional investigation into HER2 pathway alterations is needed to refine the target population for T-DM1 in NSCLC; however, HER2 IHC as a single parameter was an insufficient predictive biomarker.