FDA Approves T-DXd Plus Pertuzumab for HER2-Positive Breast Cancer

The FDA has approved trastuzumab deruxtecan (T-DXd; Enhertu) plus pertuzumab (Perjeta) for the treatment of patients with HER2-positive (HER2+) metastatic breast cancer.¹

On September 24, 2025, the FDA granted the combination priority review for the first-line treatment of patients with unresectable or metastatic HER2-positive breast cancer. T-DXd was also granted breakthrough therapy designation by the FDA in this setting.² These designations and the latest approval are based on the results of the phase 3 DESTINY-Breast09 (NCT04784715)³ trial, presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting.

Additionally, the FDA also approved the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and HER2 Dual ISH DNA Probe Cocktail as companion diagnostic devices for selecting patients with HER2+ breast cancer for treatment with T-DXd plus pertuzumab.

Results of the DESTINY-Breast09 Trial

T-DXd plus pertuzumab reduced the risk of disease progression or death by 44% vs taxane, trastuzumab, and pertuzumab (HR, 0.56; 95% CI, 0.44–0.71; P <.00001).²

The median progression-free survival (PFS) was 40.7 months in the T-DXd plus pertuzumab arm vs 26.9 months in the taxane, trastuzumab, and pertuzumab arm. The overall response rate (ORR) was 85.1% (T-DXd plus pertuzumab) vs 78.6% (taxane, trastuzumab, and pertuzumab). There were 58 complete responses observed in the T-DXd plus pertuzumab arm vs 33 in the taxane, trastuzumab, and pertuzumab arm.

The safety profile of T-DXd plus pertuzumab was consistent with the known profiles of each individual therapy with no new safety concerns identified.

A total of 1157 patients were enrolled in the trial. Patients were randomized 1:1:1 to receive either T-DXd monotherapy plus placebo, T-DXd plus pertuzumab, or taxane, trastuzumab, and pertuzumab.

The primary end point of the DESTINY-Breast09 trial was PFS and the secondary end points included PFS, overall survival, ORR, duration of response, pharmacokinetics, and safety. Patients receiving T-DXd monotherapy vs taxane, trastuzumab, and pertuzumab remains blinded to patients and investigators, and will continue to the final PFS analysis.

REFERENCES

1.FDA approves fam-trastuzumab deruxtecan-nxki with pertuzumab for unresectable or metastatic HER2-positive breast cancer. US FDA. December 15, 2025. https://tinyurl.com/bd7m9atz

2.Enhertu plus pertuzumab granted priority review in the US as 1^st-line treatment for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. Published September 24, 2025. Accessed November 18, 2025. https://tinyurl.com/4pr6u8zc

3.Trastuzumab deruxtecan (T-DXd) with or without pertuzumab versus taxane, trastuzumab and pertuzumab in HER2-positive metastatic breast cancer (DESTINY-Breast09). ClincalTrials.gov. Updated November 12, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT04784715