EMA validates a Type II variation application for ENHERTU plus pertuzumab as first-line therapy for unresectable or metastatic HER2 positive breast cancer based on DESTINY-Breast09 results.
Written By: Samiksha Jadhav BPharm
Reviewed By: Pharmacally Editorial Team
The European Medicines Agency has validated a Type II variation application seeking approval for ENHERTU in combination with pertuzumab as a first-line treatment for adults with unresectable or metastatic HER2 positive breast cancer. The decision marks the formal start of scientific review by the Committee for Medicinal Products for Human Use and follows the recent U.S. approval of the same regimen.
ENHERTU, known scientifically as trastuzumab deruxtecan, is a HER2-directed antibody drug conjugate jointly developed by Daiichi Sankyo and AstraZeneca. The therapy links a monoclonal antibody to a potent topoisomerase I inhibitor using a cleavable linker technology, allowing targeted delivery of chemotherapy directly to HER2-expressing tumor cells.
Evidence From DESTINY-Breast09
The European submission is supported by results from the phase 3 DESTINY-Breast09 trial (NCT04784715), which were presented at the 2025 American Society of Clinical Oncology meeting and later published in the New England Journal of Medicine. In the study, ENHERTU combined with pertuzumab produced a statistically significant and clinically meaningful improvement in progression-free survival compared with the long-standing standard regimen of taxane, trastuzumab and pertuzumab.
DESTINY-Breast09 enrolled 1,157 patients across multiple regions worldwide. Participants were randomized to receive either ENHERTU alone, ENHERTU plus pertuzumab, or standard THP therapy. The primary endpoint is progression-free survival assessed by blinded independent review, with overall survival, response rates, and safety as key secondary measures.
Ken Takeshita, Global Head of R&D at Daiichi Sankyo, described the validation as an important milestone. He noted that the standard of care for this setting has remained unchanged for more than ten years and emphasized the need for options that can deliver better outcomes for patients with metastatic disease.
Unmet Need in HER2 Positive Disease
Breast cancer remains one of the most common cancers worldwide, with more than two million new cases each year. Around 15 to 20 percent of metastatic breast cancers are driven by HER2 overexpression, a biologically aggressive form of the disease. Although HER2-targeted therapies have improved survival, most patients experience progression within two years of first-line treatment, and nearly one in three receive no further therapy after the initial regimen.
Expanding Role of ENHERTU
ENHERTU is already approved in more than 90 countries for previously treated HER2 positive and HER2 low breast cancer based on the DESTINY-Breast03 and DESTINY-Breast04 trials. The drug also holds indications in HER2-mutated non-small cell lung cancer, gastric and gastroesophageal junction cancers, and certain HER2-expressing solid tumors.
A broad development program continues to explore the agent as monotherapy and in combination with other cancer medicines across multiple tumor types. The ongoing EU review could open the door for its use at the very start of treatment for metastatic HER2 positive breast cancer, potentially redefining the first-line standard.
If approved, the ENHERTU and pertuzumab combination would offer European patients a new option aimed at delaying disease progression and extending survival in a setting where therapeutic advances have been limited for more than a decade.
References
ENHERTU® Plus Pertuzumab Type II Variation Application Validated in the EU as First-Line Treatment of Patients with HER2 Positive Metastatic Breast Cancer, 19 January 2026, https://www.daiichisankyo.com/files/news/pressrelease/pdf/202601/20260119_E2.pdf
Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09), ClinicalTrials.gov ID NCT04784715, https://clinicaltrials.gov/study/NCT04784715
Tolaney SM et al, Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2025 Oct 29. Epub ahead of print. PMID: 41160818. https://doi.org/10.1056/nejmoa2508668
ENHERTU, https://www.enhertu.com/