In the DESTINY-Breast09 trial, T-DXd plus pertuzumab reduced the risk of disease progression or death by 44% versus the taxane/trastuzumab/pertuzumab regimen, with a hazard ratio of 0.56 (P<0.00001).

The approval fits within the ongoing ENHERTU development program and a global collaboration between Daiichi Sankyo and AstraZeneca, with companion regulatory activity in other regions.

ENHERTU (trastuzumab deruxtecan) in combination with pertuzumab has been approved in the United States as a first-line therapy for adults with unresectable or metastatic HER2-positive breast cancer, marking the first new first-line option in more than a decade.

The trial’s primary endpoint was progression-free survival, with secondary endpoints including overall survival, objective response rate, duration of response, pharmacokinetics, and safety; final PFS results for the monotherapy arm were pending.

The trial enrolled 1,157 patients across multiple regions and stratified participants by prior treatment, hormone receptor status, and PIK3CA mutation status.

Efficacy data showed an objective response rate of 87% with ENHERTU plus pertuzumab versus 81% with standard THP therapy, with complete responses of 15% vs 8% respectively.

The drug’s broader development program spans multiple HER2-positive indications and emphasizes careful monitoring for ILD, neutropenia, and cardiac function as part of ongoing safety considerations.

Regulatory activity involved RTOR and Priority Review under a Project Orbis framework, with expedited review and international submissions coordinated across regions.

At the time of analysis, overall survival data were not mature, with 16% of patients across both study arms having died.

FDA approval for T-DXd plus pertuzumab was based on DESTINY-Breast09 results, confirming the regimen for patients with HER2-positive metastatic breast cancer.

Overall, the safety profile of the ENHERTU plus pertuzumab combination aligned with known risks of the individual drugs, with no new safety signals identified.

Safety concerns include boxed warnings for interstitial lung disease/pneumonitis and embryo-fetal toxicity; serious adverse events occurred in about 27% of patients on ENHERTU plus pertuzumab, with fatalities related to adverse reactions at 3.4%.