Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase 3 trial
Abstract
BACKGROUND
Neoadjuvant standard-of-care for HER2-positive early-stage breast cancer is trastuzumab+pertuzumab with polychemotherapy; however, existing regimens have high toxicity burdens and suboptimal outcomes. DESTINY-Breast11 assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel+trastuzumab+pertuzumab (THP) versus dose-dense doxorubicin+cyclophosphamide (ddAC) followed by THP for high-risk (≥cT3cN0 or cT0-4cN1-3), HER2-positive disease.
PATIENTS AND METHODS
This open-label, phase 3 trial (147 sites, 18 countries) randomised adults 1:1:1 to T-DXd (×8 cycles), T-DXd-THP (4+4 cycles), or ddAC-THP (4+4 cycles). T-DXd-alone arm enrolment closed early following Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population). Secondary endpoints included event-free survival (EFS; intent-to-treat population) and safety (safety analysis set).
CLINICALTRIALS
gov: NCT05113251; recruitment closed.
RESULTS
Between 25/10/2021 and 12/03/2025, 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised. pCR rates were 43·0% (T-DXd, n=123), 67·3% (T-DXd-THP, n=216), and 56·3% (ddAC-THP, n=180). T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11·2% (95% CI, 4·0, 18·3; p=0·003), with benefit in hormone receptor-positive (61·4% [n/N=145/236] vs 52·3% [n/N=123/235]; ΔpCR 9·1% [95% CI, 0·2, 17·9]) and -negative (83·1%…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 216 participants or records.
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