[Clinical Trial: Non-RCT]
Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer.
Li BT et al.
The New England Journal of Medicine. 2022 Jan 20; 386(3):241-251
https://doi.org/10.1056/NEJMoa2112431PMID: 34534430BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively.
METHODS: We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.
RESULTS: A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.
CONCLUSIONS: Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).
Copyright © 2021 Massachusetts Medical Society.
METHODS: We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.
RESULTS: A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.
CONCLUSIONS: Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).
Copyright © 2021 Massachusetts Medical Society.
- Li BT 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Smit EF 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Goto Y 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Nakagawa K 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Udagawa H 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Mazières J 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Nagasaka M 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Bazhenova L 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Saltos AN 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Felip E 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Pacheco JM 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Pérol M 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Paz-Ares L 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Saxena K 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Shiga R 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Cheng Y 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Acharyya S 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Vitazka P 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Shahidi J 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Planchard D 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- Jänne PA 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
- DESTINY-Lung01 Trial Investigators
Affiliations
- 1 From Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York (B.T.L.)
- 2 the Netherlands Cancer Institute, Amsterdam (E.F.S)
- 3 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
- 4 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
- 5 Karmanos Cancer Institute, Detroit (M.N.)
- 6 the University of California, San Diego, Moores Cancer Center, San Diego (L.B.)
- 7 Moffitt Cancer Center, Tampa, FL (A.N.S.)
- 8 Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona (E.F.)
- 9 University of Colorado, Aurora (J.M.P.)
- 10 Hospital Universitario 12 de Octubre, H12O-Centro Nacional de Investigaciones Oncológicas (CNIO) Lung Cancer Clinical Research Unit, and Complutense University, Madrid (L.P.-A.)
- 11 Daiichi Sankyo, Basking Ridge, NJ (K.S., R.S., Y.C., S.A., P.V., J.S.)
- 12 Dana-Farber Cancer Institute and the Belfer Center for Applied Cancer Science, Boston (P.A.J.)
This work was supported by:
NCI NIH HHS, United States
GrantID: R01 CA249666
NCI NIH HHS, United States
GrantID: P30 CA008748
