Purpose: HER2-targeted therapy is not standard of care for 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. Patients and Methods: Eligible patients had HER2-over-expressing NSCLC (centrally tested 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 (2þ, 3þ). 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 RECIST v1.1. Results: Forty-nine patients received T-DM1 (29 IHC 2þ, 20 IHC 3þ). No treatment responses were observed in the IHC 2þ cohort. Four partial responses were observed in the IHC 3þ cohort (ORR, 20%; 95% confidence interval, 5.7%–43.7%). Clinical benefit rates were 7% and 30% in the IHC 2þ and 3þ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free survival and overall survival were similar between cohorts. Three of 4 responders had HER2 gene amplification. No new safety signals were observed. Conclusions: T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3þ) 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.
Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non–small cell lung cancer: Efficacy, safety, and biomarkers / Peters, S., Stahel, R., Bubendorf, L., Bonomi, P., Villegas, A., Kowalski, D.M., Baik, C.S., Isla, D., De Castro Carpeno, J., Garrido, P., Rittmeyer, A., Tiseo, M., Meyenberg, C., de Haas, S., Lam, L.H., Lu, M.W., Stinchcombe, T.E.. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 25:1(2019), pp. 64-72. [10.1158/1078-0432.CCR-18-1590]
Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non–small cell lung cancer: Efficacy, safety, and biomarkers
Tiseo M.;
2019-01-01
Abstract
Purpose: HER2-targeted therapy is not standard of care for 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. Patients and Methods: Eligible patients had HER2-over-expressing NSCLC (centrally tested 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 (2þ, 3þ). 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 RECIST v1.1. Results: Forty-nine patients received T-DM1 (29 IHC 2þ, 20 IHC 3þ). No treatment responses were observed in the IHC 2þ cohort. Four partial responses were observed in the IHC 3þ cohort (ORR, 20%; 95% confidence interval, 5.7%–43.7%). Clinical benefit rates were 7% and 30% in the IHC 2þ and 3þ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free survival and overall survival were similar between cohorts. Three of 4 responders had HER2 gene amplification. No new safety signals were observed. Conclusions: T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3þ) 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
