FDA Approves Enhertu Plus Perjeta in Advanced HER2+ Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved Enhertu (fam-trastuzumab deruxtecan-nxki) in combination with Perjeta (pertuzumab) for the first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer as approved by an FDA-approved test.

The regulatory agency 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 identifying patients with HER2-positive breast cancer for treatment with Enhertu in combination with Perjeta.

The effectiveness of the treatment combination was evaluated in DESTINY-Breast09, a randomized, three-arm, multicenter global trial which evaluated 1,157 adults with HER2-positive advanced or metastatic breast cancer. Eligible patients had either not received prior chemotherapy or HER2-targeted therapy or had completed neoadjuvant or adjuvant HER2-targeted therapy more than six months before their advanced disease diagnosis. A single line of prior endocrine therapy for advanced or metastatic disease was permitted.

Patients received either the investigative combination of Enhertu plus Perjeta, THP (taxane, trastuzumab, and Perjeta), or an investigational therapy, administered via intravenous infusion every three weeks until unacceptable toxicity or disease progression.

The median progression-free survival (PFS) was 40.7 months in the Enhertu plus Perjeta arm versus 26.9 months in the THP arm. The confirmed objective response rates were 87% and 81%, respectively. At the time of the PFS analysis, overall survival data were not mature, with 126 patients (16%) having died across both arms, according to the FDA.

The agency also went on to share in their release that the prescribing information for the treatment combination includes warnings and precautions for neutropenia and left ventricular dysfunction.

The recommended Enhertu dose for day one of the first cycle is 5.4 milligrams per kilogram (mg/kg), followed by 840 mg of Perjeta. For subsequent cycles, the recommended dose of Enhertu is 5.4 mg/kg, followed by Perjeta 420 mg via intravenous (IV) infusion every three weeks.

Study Findings Presented at SABCS

Earlier this month, researchers reported that patients with HER2-positive advanced or metastatic breast cancer who were treated with the Enhertu and Perjeta combination had better quality-of-life and fewer gastrointestinal, skin and mucosal side effects than those receiving the standard-of-care. This information was shared in the patient-reported data from the phase 3 DESTINY-Breast09 trial which was presented at the 2025 San Antonio Breast Cancer Symposium.

“Patients reported that the Enhertu [combination] was similarly tolerable over time,” Dr. Mothaffar F. Rimawi, of the Dan L. Duncan Comprehensive Cancer Center and Baylor College of Medicine in Houston, Texas, said during the presentation. “The risk of clinically meaningful deterioration was similar, although data are still immature at this interim analysis.”

Patients receiving Enhertu plus Perjeta had more gastrointestinal side effects, including nausea, vomiting, constipation, and appetite loss, but fewer skin and mucosal effects, nosebleeds, and extremity swelling. 

Patients in both arms reported similar levels of pain control, fatigue and overall treatment tolerability. The majority of patients on both treatments successfully maintained or improved physical function throughout the study.

What Are Enhertu and Perjeta?

Enhertu, according to the National Cancer Institute, is a targeted therapy known as an antibody-drug conjugate. It combines a monoclonal antibody that binds to HER2 on cancer cells with deruxtecan, a drug that enters these cells and causes DNA damage, leading to cell death. 

Perjeta, the National Cancer Institute explained, binds to HER2 and causes cancer cells to stop growing and die. It is a type of targeted therapy drug known as a monoclonal antibody.

References

1. "FDA approves fam-trastuzumab deruxtecan-nxki with pertuzumab for unresectable or metastatic HER2-positive breast cancer," by the U.S. FDA. News release; Dec. 15, 2025.
2. "Enhertu/Perjeta Combo Enhances Quality of in HER2+ Advanced Breast Cancer," by Paige Britt. CURE; Dec. 11, 2025. https://www.curetoday.com/view/enhertu-perjeta-combo-enhances-quality-of-in-her2-advanced-breast-cancer
3. "Fam-Trastuzumab Deruxtecan-nxki," by the National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/famtrastuzumabderuxtecan-nxki
4. "Pertuzumab," by the National Cancer Institute; https://www.cancer.gov/about-cancer/treatment/drugs/pertuzumab

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