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

In In The News by Barbara Jacoby

By: Paige Britt

From: targetedonc.com

Key Takeaways

  • The FDA approved T-DXd plus pertuzumab for HER2-positive metastatic breast cancer, based on DESTINY-Breast09 trial results.
  • The combination therapy reduced disease progression or death risk by 44% compared to the standard regimen.
  • Median progression-free survival was 40.7 months, with an overall response rate of 85.1% for T-DXd plus pertuzumab.
  • The safety profile of the combination was consistent with known profiles, with no new safety concerns identified.

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 1st-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