FDA Approves enhertu Combination for First-Line HER2-Positive Breast cancer Treatment

The FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd, Enhertu; Daiichi Sankyo, Inc.) in combination with pertuzumab (Perjeta; Genentech) for the first-line treatment of adults with unresectable or metastatic HER2-positive (HER2+; IHC 3+ or ISH+) breast cancer as determined by an FDA-approved test.

Simultaneously, 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 HER2-positive (HER2 IHC3+ or ISH+) breast cancer patients for treatment with T-DXd in combination with pertuzumab.¹

!X-ray of breast cancer — Image credit: Sebastian Kaulitzki | stock.adobe.com
Image credit: Sebastian Kaulitzki | stock.adobe.com

The Phase 3 DESTINY-Breast09 Clinical Trial

The approval is supported by positive findings from the randomized,3-arm,multicenter,global phase 3 clinical trial,DESTINY-Breast09 (NCT04784715),which compared T-DXd with or without pertuzumab to taxane,trastuzumab (Herceptin; Genentech),and pertuzumab (THP).

The trial consisted of 1157 adults with HER2+ advanced or metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than 6 months prior to the diagnosis of advanced or metastatic disease.²

FDA Approves new Treatment Combination for HER2-Positive Breast cancer

The Food and Drug Governance (FDA) recently approved a new combination therapy for patients with unresectable or metastatic HER2-positive breast cancer. The treatment combines fam-trastuzumab deruxtecan-nxki (enhertu) with pertuzumab. This approval offers a new option for individuals whose cancer has progressed after prior anti-HER2 therapies.

Previously, patients with HER2-positive breast cancer who had received prior anti-HER2 treatments faced limited options.The DESTINY-Breast09 clinical trial (NCT04784715) demonstrated significant benefits with trastuzumab deruxtecan (T-DXd), with or without pertuzumab, compared to standard taxane, trastuzumab, and pertuzumab regimens. The trial, updated as of November 12, 2025, showed improved progression-free survival and overall survival in patients treated with the new combination.

Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody drug conjugate. It delivers a potent chemotherapy agent directly to cancer cells, minimizing exposure to healthy tissues. Pertuzumab is another HER2-targeted therapy that enhances the effectiveness of trastuzumab.

This approval represents a significant advancement in the treatment of HER2-positive breast cancer, offering renewed hope for patients facing this challenging diagnosis.

FDA Approves Fam-Trastuzumab Deruxtecan-Nxki and Pertuzumab for Unresectable or Metastatic HER2-Positive Breast cancer

2. Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic breast Cancer (DESTINY-Breast09). ClinicalTrials.gov identifier: NCT04784715. Updated November 12,2025. Accessed December 15, 2025.