Patient-reported outcomes with T-DXd + pertuzumab in HER2+ MBC (DESTINY-Breast09)

In this video, Prof Dr François Duhoux reviews the patient-reported outcomes (PROs) from the phase III DESTINY-Breast09 trial in first-line HER2-positive metastatic breast cancer, comparing trastuzumab deruxtecan (T-DXd) + pertuzumab with standard taxane + trastuzumab + pertuzumab (THP). 

DESTINY-Breast09 previously demonstrated a progression-free survival benefit for T-DXd + pertuzumab versus THP. The PRO analysis presented at SABCS 2025 assessed tolerability and quality of life using validated tools, including the Patient Global Impression of Treatment Tolerability (PGI-TT) and the EORTC QLQ-C30 questionnaire. 

Overall, patient-reported tolerability was similar between both treatment arms, despite early discontinuation of the taxane component in the THP arm. No differences were observed in the risk of clinically meaningful deterioration in pain, and outcomes for fatigue and physical functioning were broadly comparable. 

However, distinct symptom profiles were reported: T-DXd + pertuzumab was associated with more nausea, vomiting, constipation, and appetite loss than THP, with similar impact on diarrhoea. 

Taken together, these PRO results support T-DXd + pertuzumab as a well-tolerated first-line option in HER2-positive metastatic breast cancer, complementing the efficacy outcomes from DESTINY-Breast09.