Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer
Bob T Li1, Egbert F Smit1, Yasushi Goto1
1From Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York (B.T.L.); the Netherlands Cancer Institute, Amsterdam (E.F.S); the National Cancer Center Hospital, Tokyo (Y.G.), Kindai University Hospital, Osaka (K.N.), and the National Cancer Center East, Kashiwa (H.U.) - all in Japan; Centre Hospitalier Universitaire, Toulouse (J.M.), Centre Léon Bérard, Lyon (M.P.), and the Department of Medical Oncology, Thoracic Group, Gustave Roussy, Villejuif (D.P.) - all in France; Karmanos Cancer Institute, Detroit (M.N.); the University of California, San Diego, Moores Cancer Center, San Diego (L.B.); Moffitt Cancer Center, Tampa, FL (A.N.S.); Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona (E.F.); University of Colorado, Aurora (J.M.P.); Hospital Universitario 12 de Octubre, H12O-Centro Nacional de Investigaciones Oncológicas (CNIO) Lung Cancer Clinical Research Unit, and Complutense University, Madrid (L.P.-A.); Daiichi Sankyo, Basking Ridge, NJ (K.S., R.S., Y.C., S.A., P.V., J.S.); and Dana-Farber Cancer Institute and the Belfer Center for Applied Cancer Science, Boston (P.A.J.).
Trastuzumab deruxtecan demonstrated significant anticancer activity in patients with previously treated HER2-mutant non-small-cell lung cancer. While effective, the treatment carries risks, including fatal interstitial lung disease in some cases.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- HER2-targeted therapies lack approval for non-small-cell lung cancer (NSCLC).
- Efficacy and safety of trastuzumab deruxtecan in HER2-mutant NSCLC remain under-investigated.
Purpose of the Study:
- To evaluate the efficacy and safety of trastuzumab deruxtecan in patients with metastatic HER2-mutant NSCLC.
- To assess objective response, duration of response, progression-free survival, overall survival, and safety outcomes.
Main Methods:
- A multicenter, international, phase 2 study.
- Trastuzumab deruxtecan (6.4 mg/kg) administered to patients with refractory HER2-mutant NSCLC.
- Independent central review for objective response assessment; biomarker analysis for HER2 alterations.
Main Results:
- Objective response observed in 55% of 91 patients; median response duration 9.3 months.
- Median progression-free survival of 8.2 months and overall survival of 17.8 months.
- Drug-related adverse events in 46% (neutropenia 19%); fatal interstitial lung disease in 2 patients (26% incidence).
Conclusions:
- Trastuzumab deruxtecan exhibits durable anticancer activity in previously treated HER2-mutant NSCLC.
- The safety profile is consistent with prior studies, but includes fatal interstitial lung disease.
- Responses were noted across various HER2 mutation subtypes and expression levels.
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