ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Emerging role of human epidermal growth factor 2-low status in the prognosis and management of triple-negative breast cancer: a narrative review.Translational cancer research · 2026Review
- Precision immunotherapy for breast cancer: from biomarkers to clinical practice.Cancer biology & medicine · 2026Article
- Case Report: Trastuzumab deruxtecan combined with fulvestrant in a patient with HR+/HER2-low metastatic breast cancer.Frontiers in oncology · 2026Article
- HER2-Targeted Antibody-Drug Conjugates in Advanced HER2-Low Breast Cancer: Mechanisms, Clinical Efficacy, and Resistance Strategies.Cancer management and research · 2026Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
purposeEstablish the safety, tolerability, and preliminary activity of trastuzumab deruxtecan (T-DXd) in combination with other anticancer therapies in human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). PATIENTS AND
methodsDESTINY-Breast08 was a two-part, open-label, multicenter, phase Ib study. Patients with locally confirmed HER2-low mBC received T-DXd plus capecitabine, durvalumab + paclitaxel, capivasertib, anastrozole, or fulvestrant. Eligibility criteria for hormone receptor status varied across modules and between study parts. Primary objectives were safety/tolerability and determining recommended phase II doses (RP2D); secondary endpoints included objective response rate (ORR; per investigator).
resultsIn the dose-finding phase, 37 patients were assigned to a module. RP2Ds were determined for T-DXd plus capecitabine, capivasertib, anastrozole, or fulvestrant. For strategic reasons, T-DXd + durvalumab + paclitaxel was not pursued beyond the dose-finding phase (n = 3). In the dose-expansion phase, 101 patients were assigned to a module. For T-DXd + capecitabine, grade ≥3 adverse events (AE) occurred in 55% (11/20) of patients, and the ORR was 60%. For T-DXd + capivasertib, grade ≥3 AEs occurred in 67.5% (27/40) of patients, and the ORR was 60%. For T-DXd + anastrozole, grade ≥3 AEs occurred in 47.6% (10/21) of patients, and the ORR was 71.4%. For T-DXd + fulvestrant, grade ≥3 AEs occurred in 55% (11/20) of patients, and the ORR was 40%. Adjudicated drug-related interstitial lung disease/pneumonitis events were reported for T-DXd + capecitabine (3/20; grade 2, n = 2; grade 5, n = 1), T-DXd + capivasertib (8/40; all grade ≤2), and T-DXd + fulvestrant (5/20; all grade 2).
conclusionsSafety results were generally consistent with known individual profiles for T-DXd and combination drugs. T-DXd plus capecitabine, capivasertib, anastrozole, or fulvestrant demonstrated preliminary clinical activity in patients with HER2-low mBC.
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