T-DXd Regimen Improves pCR in Early HER2+ Breast Cancer

These results mark the first phase 3 data to exhibit T-DXd's affect in early HER2-positive breast cancer.

Patients with high-risk, locally advanced, HER2-positive early breast cancer experienced a clinically meaningful and statistically significant improvement in pathologic complete response (pCR) when treated with neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP), according to high-level results from the phase 3 DESTINY-Breast11 trial (NCT05113251).¹

This marks the first phase 3 study to demonstrate benefits of T-DXd in early breast cancer, and achieving a pCR in early-stage HER2-positive breast cancer is associated with better long-term outcomes.

“The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of [T-DXd] to challenge the current standard of care in early-stage HER2-positive breast cancer. [T-DXd] is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible,” said Susan Galbraith, executive vice president of oncology hematology research and development at AztraZeneca, in a press release.

Data for the secondary end point of event-free survival (EFS) were not mature at the time of this analysis; however, there was an early positive trend for EFS in the T-DXd arm vs the standard of care of doxorubicin and cyclophosphamide followed by THP.

Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities.

About DESTINY-Breast11

DESTINY-Breast11 is a randomized, open-label, phase 3 study comparing T-DXd vs doxorubicin and cyclophosphamide followed by THP before surgery in patients with high-risk, HER2-positive, early-stage breast cancer.² A third arm evaluating T-DXd alone was initially included in the study; however, this arm was closed following recommendations from an independent committee.¹

The primary end point is pCR, and secondary end points include EFS, invasive disease-free survival, and overall survival.²

Patients were enrolled at 146 global sites. To be eligible, patients were required to be at least 18 years of age, have histologically documented HER2-positive early breast cancer, have an ECOG performance status of 0 or 1, and have adequate organ and bone marrow function.

About T-DXd

T-DXd is a HER2-directed antibody-drug conjugate and currently approved in over 75 countries for the treatment of unresectable or metastatic HER2-positive breast cancer that has been treated with at least 1 anti-HER2-based regimen. Its approval was supported by results from the DESTINY-Breast03 study (NCT03529110).¹

In April 2025, findings from DESTINY-Breast09 (NCT04784715) showed that T-DXd plus pertuzumab led to a highly statistically significant and clinically meaningful improvement in progression-free survival vs THP for the treatment of patients with first-line, HER2-positive, metastatic breast cancer.³

References

1. Enhertu followed by THP before surgery showed statistically significant and clinically meaningful improvement in pathologic complete response in patients with high-risk HER2-positive early-stage breast cancer in DESTINY-Breast11 phase III trial. News release. AstraZeneca. May 7, 2025. Accessed May 7, 2025. https://tinyurl.com/42u3y2y3
2. Trastuzumab deruxtecan (T-DXd) alone or in sequence with THP, versus standard treatment (ddAC-THP), in HER2-positive early breast cancer. ClinicalTrials.gov. Updated May 6, 2025. Accessed May 7, 2025. https://clinicaltrials.gov/study/NCT05113251
3. ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed May 7, 2025. https://tinyurl.com/3fv3ydxe