EMA Begins Review of Trastuzumab Deruxtecan Plus Pertuzumab as First-Line Therapy for HER2 Positive Metastatic Breast Cancer | iPharmaCenter

The European Medicines Agency (EMA) has accepted for review a Type II variation application for trastuzumab deruxtecan in combination with pertuzumab as an initial treatment option for adults with unresectable or metastatic HER2 positive breast cancer. The antibody drug conjugate, discovered by Daiichi Sankyo and co‑developed and co‑commercialized with AstraZeneca, is already authorized in later‑line HER2 positive settings, and this filing seeks to move the regimen into the first‑line metastatic space.

The EMA validation confirms that the submission is complete and triggers a scientific assessment by the Committee for Medicinal Products for Human Use (CHMP). The application is built on results from the phase 3 DESTINY‑Breast09 trial.

In that study, trastuzumab deruxtecan plus pertuzumab produced a statistically significant and clinically meaningful improvement in progression‑free survival compared with the current first‑line standard regimen of taxane, trastuzumab and pertuzumab (THP) in patients with HER2 positive metastatic disease.

DESTINY‑Breast09 is a global, randomized, open‑label phase 3 study in previously untreated HER2 positive metastatic breast cancer, comparing trastuzumab deruxtecan alone, trastuzumab deruxtecan plus pertuzumab, and control THP. Patients were assigned in equal proportions and stratified by de novo versus recurrent metastatic disease, hormone receptor status and PIK3CA mutation, with independently assessed progression‑free survival as the primary endpoint for both the monotherapy and combination arms. While the combination results versus THP have been reported, the monotherapy comparison remains blinded and will continue to the final progression‑free survival readout.

Breast cancer remains one of the most commonly diagnosed cancers and a major cause of cancer death worldwide, with more than two million new cases and over 665,000 deaths estimated globally in 2022, including around 557,000 diagnoses and over 144,000 deaths in Europe alone.

Despite substantial gains in outcomes for early‑stage disease, only about 30% of patients living with metastatic breast cancer are expected to survive for five years after diagnosis, highlighting the need for more effective first‑line options in aggressive subtypes such as HER2 positive metastatic disease.