Enhertu/Perjeta Combo Enhances Quality of in HER2+ Advanced Breast Cancer

Patients with HER2-positive advanced or metastatic breast cancer who received fam-trastuzumab deruxtecan (Enhertu) plus pertuzumab (Perjeta) reported better quality-of-life and fewer gastrointestinal, skin, and mucosal side effects than those receiving the standard-of-care, according to patient-reported data from the phase 3 DESTINY-Breast09 trial.

Data were presented at the 2025 San Antonio Breast Cancer Symposium by Dr. Mothaffar F. Rimawi, Dan L. Duncan Comprehensive Cancer Center and Baylor College of Medicine, Houston, Texas.

The DESTINY-Breast09 trial compared Enhertu plus Perjeta to the standard-of-care regimen of trastuzumab (Herceptin), Perjeta, and taxane as first-line therapy for patients with HER2-positive advanced or metastatic breast cancer. Previous results show that Enhertu plus Perjeta improved progression-free survival.

In September 2025, the FDA granted priority review to the supplemental biologics license application of Enhertu for first-line treatment of patients with unresectable or metastatic HER2-positive breast cancer.

In total, 383 patients received 5.4 mg/kg of Enhertu once every 3 weeks plus an 840 mg loading dose of Perjeta followed by 420 mg once every 3 weeks. In the trastuzumab, Perjeta, and taxane arm, 387 patients received the standard-of-care combination of the three drugs.

Patient-Reported Outcomes Highlight Differences in Side Effects 

Compared with trastuzumab, Perjeta, and taxane, Enhertu plus Perjeta presents a distinct quality-of-life profile. Patients receiving Enhertu plus Perjeta experienced more gastrointestinal side effects, including nausea, vomiting, constipation, and appetite loss. This group also experienced fewer issues with skin and mucosal side 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.

The patient-reported end points included time to deterioration in pain, proportion of patients experiencing deterioration in treatment-related symptoms, proportion of patients with maintained or improved physical function, and overall side effect burden as reported by patients.

Impact on pain and physical function was largely similar between the Enhertu plus Perjeta arm and the trastuzumab, Perjeta, and taxane arm. Median time to deterioration in pain was not reached in either treatment arm.

A high percentage of patients in both arms maintained or improved physical function. At cycle 2, 83% of patients in the Enhertu plus Perjeta arm (328 patients) maintained or improved physical function versus 82% of patients in the trastuzumab, Perjeta, and taxane arm (341 patients). At cycle 27 (18.7 months), 75% of patients in the Enhertu plus Perjeta arm (187 patients) maintained or improved physical function versus 78% in the trastuzumab, Perjeta, and taxane arm (166 patients).

Primary differences in patient experience emerged in specific side effects. Patients in the Enhertu plus Perjeta arm experienced more gastrointestinal issues, specifically nausea and vomiting (49% versus 30%). Conversely, patients in this arm reported less deterioration in skin and mucosal side effects, including nosebleeds and extremity swelling (23% versus 34% at cycle 2; 37% versus 42% at cycle 27). Deterioration in fatigue was comparable between both arms at cycles 2 (41% versus 42%) and 27 (38% versus 36%). Overall treatment tolerability was similar between the regimens.

Key Takeaways for Patients and Physicians from DESTINY-Breast09

The patient-reported outcomes from DESTINY-Breast09 provide crucial context to the primary efficacy and safety results. The data conclude that Enhertu plus Perjeta offers durable pain control and allows maintenance of physical function, outcomes comparable to the standard-of-care trastuzumab, Perjeta, and taxane regimen.

“Patients reported Enhertu and [trastuzumab, Perjeta, and taxane] as similarly tolerable over time,” Rimawi concluded during the presentation. “The risk of clinically meaningful deterioration was similar, although data are still immature at this interim analysis.”

References

1. “Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for first-line treatment of patients with HER2+ advanced/metastatic breast cancer: patient-reported outcomes from the DESTINY-Breast09 study,” by Dr. Mothaffar F. Rimawi. Presentation RF6-07. San Antonio Breast Cancer Symposium. Dec. 10, 2025.
2. “Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with HER2-positive (HER2+) advanced/metastatic breast cancer (a/mBC): patient-reported outcomes (PROs) from the DESTINY-Breast09 study,” by Dr. Mothaffar F. Rimawi. Presented at the San Antonio Breast Cancer Symposium. Dec. 10, 2025.

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