Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial
Yet another combination to consider after CDK4/6i + ET in HR+ MBC!
Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
Author(s): Aditya Bardia, M.D., Xichun Hu, M.D., Ph.D., Rebecca Dent, M.D., Kan Yonemori, M.D., Carlos H. Barrios, M.D., Joyce A. O’Shaughnessy, M.D., Hans Wildiers, M.D., Ph.D., Jean-Yves Pierga, M.D., Ph.D., Qingyuan Zhang, M.D., Ph.D., Cristina Saura, M.D., Ph.D., Laura Biganzoli, M.D., Joohyuk Sohn, M.D., Ph.D. https://orcid.org/0000-0002-2303-2764, Seock-Ah Im, M.D., Ph.D., Christelle Lévy, M.D., William Jacot, M.D., Ph.D., Natasha Begbie, M.B., B.S., M.Res., Jun Ke, Ph.D., Gargi Patel, M.B., B.Chir., Ph.D., and Giuseppe Curigliano, M.D., Ph.D. https://orcid.org/0000-0003-1781-2518, for the DESTINY-Breast06 Trial Investigators*
Source: N Engl J Med 2024;391:2110-2122
Dr. Maen Hussein's Thoughts
TD beat chemotherapy after failure of hormonal therapy in HER-2 low and ultra low. Wait for the indication.
BACKGROUND
Outcomes in patients with hormone receptor–positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.
METHODS
We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor–positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician’s choice of chemotherapy. The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. Secondary end points included progression-free survival among all the patients who had undergone randomization, overall survival, and safety.
RESULTS
Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease. Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75; P<0.001); the results were consistent in the exploratory HER2-ultralow population. Data for overall survival were immature. Adverse events of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan group and in 44.4% of those in the chemotherapy group. Adjudicated interstitial lung disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in severity) and in 1 patient (0.2%; grade 2), respectively.
CONCLUSIONS
Among patients with hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer who had received one or more lines of endocrine-based therapy, treatment with trastuzumab deruxtecan resulted in longer progression-free survival than chemotherapy. No new safety signals were identified. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast06 ClinicalTrials.gov number, NCT04494425.)
Author Affiliations
From 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.).Related Articles
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