Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
Aditya Bardia1, Xichun Hu1, Rebecca Dent1
1From Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, and Massachusetts General Hospital, Boston, MA (A.B.); the Department of Medical Oncology, Fudan University Shanghai Cancer Center, and the Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (X.H.), and Harbin Medical University Cancer Hospital, Harbin (Q.Z.) - all in China; the Division of Medical Oncology, National Cancer Center Singapore, Singapore (R.D.); National Cancer Center Hospital, Tokyo (K.Y.); the Latin American Cooperative Oncology Group, Porto Alegre, Brazil (C.H.B.); Texas Oncology and US Oncology, Baylor University Medical Center, Dallas (J.A.O.); the Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium (H.W.); the Department of Medical Oncology, Institut Curie and Université Paris Cité, Paris (J.-Y.P.), Centre François Baclesse, Caen (C.L.), and the Department of Medical Oncology, Institut du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier (W.J.) - all in France; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (C.S.); the Department of Oncology, Santo Stefano Hospital, Azienda Unità Sanitaria Locale Toscana Centro, Prato (L.B.), and the European Institute of Oncology, IRCCS, and the Department of Oncology and Hematology-Oncology, University of Milan, Milan (G.C.) - all in Italy; the Division of Medical Oncology, Yonsei Cancer Center (J.S.), and the Department of Internal Medicine, Seoul National University Hospital (S.-A.I.) - both in Seoul, South Korea; Clinical Development, Late-Stage Development, Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom (N.B., G.P.); and Biometrics Oncology, Late-Stage Development, Oncology Research and Development, AstraZeneca, Waltham, MA (J.K.).
Trastuzumab deruxtecan significantly improved progression-free survival in patients with hormone receptor-positive, HER2-low metastatic breast cancer compared to chemotherapy. This offers a new treatment option for patients who have undergone prior endocrine therapy.
Area of Science:
- Oncology
- Medical research
Background:
- Hormone receptor-positive metastatic breast cancer outcomes decline after endocrine therapy.
- Trastuzumab deruxtecan shows promise in HER2-low metastatic breast cancer post-chemotherapy.
Purpose of the Study:
- To evaluate the efficacy of trastuzumab deruxtecan versus chemotherapy in patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer.
- To assess progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints.
Main Methods:
- Phase 3, multicenter, open-label trial comparing trastuzumab deruxtecan to physician's choice of chemotherapy.
- Randomized 1:1 assignment for patients with HER2-low (IHC 1-2+, ISH-) or HER2-ultralow (IHC 0) metastatic breast cancer previously treated with endocrine therapy.
- Primary endpoint: PFS in HER2-low population; Secondary endpoints: PFS in all randomized patients, OS, and safety.
Main Results:
- Median PFS was 13.2 months with trastuzumab deruxtecan vs. 8.1 months with chemotherapy in HER2-low patients (HR 0.62, P<0.001).
- Consistent results observed in the HER2-ultralow subgroup.
- Grade 3+ adverse events occurred in 52.8% (trastuzumab deruxtecan) vs. 44.4% (chemotherapy); adjudicated interstitial lung disease/pneumonitis in 11.3% vs. 0.2%.
Conclusions:
- Trastuzumab deruxtecan demonstrated superior PFS compared to chemotherapy in hormone receptor-positive, HER2-low/ultralow metastatic breast cancer patients after endocrine therapy.
- No new safety concerns were identified with trastuzumab deruxtecan.
- The study provides evidence for trastuzumab deruxtecan as an effective treatment option in this patient population.
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