News Report · Oncology

FDA Approves Trastuzumab Deruxtecan for Neoadjuvant HER2-Positive Breast Cancer: 67.3% pCR in DESTINY-Breast11 Trial

June 07, 2026

pCR Rate

67.3%

Trial Enrollment

927 patients

Clinical Perspective

The recent FDA approval of trastuzumab deruxtecan for neoadjuvant HER2-positive breast cancer provides a significant advancement in treatment options for high-risk patients. The impressive pCR rate of 67.3% in the DESTINY-Breast11 trial highlights its potential to improve surgical outcomes and reduce recurrence rates. This approval may reshape treatment protocols and patient selection in clinical practice.

Dr. Meera Pillai · Oncology

Trastuzumab deruxtecan (Enhertu) reduced the pathologic complete response (pCR) rate by 67.3% versus doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab in patients with HER2-positive early-stage breast cancer in the DESTINY-Breast11 trial (p-value 0.003) [1].

Clinical Context

HER2-positive breast cancer is characterized by overexpression of the HER2 protein, leading to aggressive disease and poor prognosis. Approximately 15-20% of breast cancer cases are HER2-positive, which significantly impacts treatment decisions and outcomes. Current standard treatments include chemotherapy combined with HER2-targeted therapies like trastuzumab and pertuzumab. However, many patients still experience disease recurrence, indicating a need for more effective neoadjuvant options. The recent approval of trastuzumab deruxtecan aims to address this gap, providing a new therapeutic avenue for patients with high-risk, early-stage HER2-positive breast cancer.

Key Findings

The DESTINY-Breast11 trial showed trastuzumab deruxtecan followed by THP reduced pCR by 67.3% versus doxorubicin and cyclophosphamide followed by THP (p-value 0.003) [1].
The trial enrolled 927 adults with HER2-positive, high-risk, early-stage breast cancer [1].
Event rates: 67.3% pCR in the T-DXd-THP arm versus 56.3% in the ddAC-THP arm [1].
The primary endpoint was the pCR rate, defined as the absence of invasive cancer in the breast and axillary lymph nodes following surgery [1].
Secondary endpoints included event-free survival (EFS) and overall survival (OS), but results were not statistically controlled or powered [1].
Trastuzumab deruxtecan is administered at a dose of 5.4 mg/kg by intravenous infusion every three weeks [1].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis reported with trastuzumab deruxtecan — monitor throughout treatment and for at least 5 months after last dose [1].
Severe or fatal immune-mediated reactions occurred — withhold or permanently discontinue based on severity [1].
Infusion-related reactions reported — monitor during and after each infusion [1].
Embryo-fetal toxicity — advise patients of reproductive potential to use effective contraception [1].
Discontinuation rates due to adverse events not available in public source summary.
Complete adverse event profile available in the full prescribing information for trastuzumab deruxtecan (Enhertu) [1].

What This Means for Clinical Practice

Trastuzumab deruxtecan is used in adults with HER2-positive early-stage breast cancer who are eligible for neoadjuvant treatment. The 67.3% pCR rate supports its use in this high-risk population, potentially improving surgical outcomes. How this approval will influence treatment protocols and patient selection in clinical practice remains to be established?

Study Design

DESTINY-Breast11 was a randomized, three-arm, open-label, multicenter trial that enrolled 927 adults with HER2-positive, high-risk, early-stage breast cancer. Patients were randomized (1:1:1) to receive eight cycles of neoadjuvant treatment with trastuzumab deruxtecan followed by THP, doxorubicin and cyclophosphamide followed by THP, or an additional investigational therapy. The major efficacy outcome measure was centrally assessed pathological complete response (pCR) rate, with a follow-up duration until completion of planned therapy or disease progression. The study was funded by Daiichi Sankyo, Inc. Key limitations include the lack of statistical control for secondary endpoints and the reliance on a single trial for the primary indication. Further data on long-term outcomes and comparative effectiveness with other regimens is still pending.

References

FDA — FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. Date published: May 15, 2026. URL: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage
FDA — Oncology (Cancer)/Hematologic Malignancies Approval Notifications. Date published: May 15, 2026. URL: https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications

FAQ

Q: What is trastuzumab deruxtecan (Enhertu) approved for?

A: Trastuzumab deruxtecan is approved for the neoadjuvant treatment of adults with HER2-positive early-stage breast cancer, as well as for adjuvant treatment in patients with residual invasive disease after neoadjuvant therapy. The FDA approved it on May 15, 2026, based on the DESTINY-Breast11 trial demonstrating a 67.3% pCR rate versus standard treatment [1].

Q: How does trastuzumab deruxtecan work?

A: Trastuzumab deruxtecan is an antibody-drug conjugate that targets the HER2 protein, delivering cytotoxic chemotherapy directly to HER2-expressing cancer cells. This mechanism enhances the efficacy of treatment compared to traditional therapies that do not specifically target HER2. It is part of a new generation of targeted therapies for breast cancer.

Q: What is the recommended dose of trastuzumab deruxtecan?

A: The recommended dose of trastuzumab deruxtecan is 5.4 mg/kg administered by intravenous infusion every three weeks. Clinicians should consult current prescribing information for full dosing guidance. Clinicians should consult the current prescribing information for full dosing guidance [1].

Q: What are the most common side effects of trastuzumab deruxtecan?

A: Common side effects include immune-mediated adverse reactions, infusion-related reactions, and embryo-fetal toxicity. Specific frequencies of adverse events are not available in the public source summary, and healthcare professionals are advised to refer to the prescribing information for a complete adverse event profile [1].

FDA Approves Trastuzumab Deruxtecan for Neoadjuvant HER2-Positive Breast Cancer: 67.3% pCR in DESTINY-Breast11 Trial

FDA Approves Trastuzumab Deruxtecan for Neoadjuvant HER2-Positive Breast Cancer: 67.3% pCR in DESTINY-Breast11 Trial

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

What This Means for Clinical Practice

Study Design

References

FAQ

References

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