The European Commission has approved trastuzumab deruxtecan in combination with pertuzumab for the first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer, AstraZeneca and Daiichi Sankyo announced on September 1, 2026.
The indication covers patients with HER2-positive disease defined as immunohistochemistry (IHC) 3+ or in-situ hybridization (ISH)+. The decision follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use and represents the first new first-line regimen approved in the EU for this patient population in more than a decade.
The approval is based on results from the Phase 3 DESTINY-Breast09 trial, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting and subsequently published in The New England Journal of Medicine (DOI: 10.1056/NEJMoa2508668).
DESTINY-Breast09: The Trial Changing the Future of HER2-Positive Breast Cancer
DESTINY-Breast09: PFS Exceeds Three Years
DESTINY-Breast09 is a global, multicenter, randomized, open-label Phase 3 trial evaluating trastuzumab 5.4 mg/kg alone or in combination with pertuzumab versus standard-of-care taxane, trastuzumab and pertuzumab (THP) as first-line treatment for HER2-positive metastatic breast cancer. The trial enrolled 1,157 patients across Africa, Asia, Europe, North America and South America.
In the comparison supporting the approval, 383 patients received trastuzumab plus pertuzumab. The combination reduced the risk of disease progression or death by 44% compared with THP:
- Hazard ratio: 0.5
- 95% CI: 0.44–0.71
- p-value: <0.00001
- Median PFS: 40.7 months with trastuzumab plus pertuzumab vs 26.9 months with THP
- Confirmed ORR: 85.1% vs 78.6%, respectively.
Patients included in this analysis had not received previous chemotherapy or HER2-targeted therapy for metastatic disease, or had received neoadjuvant or adjuvant HER2-targeted treatment more than six months before diagnosis of advanced or metastatic disease.
Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology and a steering committee member and investigator for DESTINY-Breast09, said:
“The combination of trastuzumab deruxtecan and pertuzumab represents a significant therapeutic advance.”
She said maintaining disease control for as long as possible is a critical objective in first-line HER2-positive metastatic breast cancer and highlighted that progression-free survival with the combination exceeded three years compared with approximately two years with the current standard of care.
A New First-Line Option After More Than a Decade
HER2-positive metastatic breast cancer is driven by HER2 overexpression or amplification and accounts for approximately 15% to 20% of metastatic breast cancers. THP has been the standard first-line regimen for more than a decade, but the companies noted that most patients experience disease progression within two years of treatment. Approximately one in three patients do not receive another therapy after first-line treatment because of disease progression or death.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said:
“This approval brings trastuzumab to patients in the EU earlier in the course of their metastatic disease.”
Fredrickson added that the approval sets a new benchmark for progression-free survival in the first-line setting and emphasized the importance of starting effective HER2-directed therapy early in the disease course.
Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., said the approval has the potential to reshape clinical practice in first-line HER2-positive metastatic breast cancer. He also noted that this is the second new EU indication for trastuzumab in two months, following its recent tumor-agnostic approval.
Trastuzumab Plus Pertuzumab Added to ESMO Guidelines
Based on the DESTINY-Breast09 findings, trastuzumab plus pertuzumab has been included in the ESMO Clinical Practice Guidelines as a Category IA first-line treatment option for patients with metastatic HER2-positive breast cancer, regardless of hormone receptor status.
Trastuzumab is also under review in the EU for patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant HER2-targeted treatment, based on results from the DESTINY-Breast05 trial.
Safety of trastuzumab Plus Pertuzumab
The safety profile of trastuzumab plus pertuzumab was consistent with the known safety profiles of the individual treatments, with no new safety concerns identified.
In a pooled safety analysis of 431 patients with unresectable or metastatic breast cancer treated with trastuzumab plus pertuzumab across two trials, Grade 3 or 4 adverse reactions included neutropenia (24.8%), hypokalemia (13.2%), anemia (10.7%), diarrhea (7.4%), fatigue (7.2%) and thrombocytopenia (7.0%). Grade 5 adverse reactions occurred in 1.6% of patients, including pneumonia, interstitial lung disease/pneumonitis, dyspnea and febrile neutropenia.
EU Approval Follows First-Line Approval in China
The European decision follows the August 2026 approval of trastuzumab plus pertuzumab in China for first-line unresectable or metastatic HER2-positive breast cancer, also based on DESTINY-Breast09.
As previously reported by OncoDaily, China’s National Medical Products Administration approved the combination after the trial demonstrated the same 44% reduction in the risk of progression or death compared with THP. The China approval was the fourth new trastuzumab indication in the country in less than a year, bringing the medicine to eight approved indications there.
In that announcement, Mary Guan, General Manager of China Oncology Business at AstraZeneca, said:
“DESTINY-Breast09 sets a new benchmark for progression-free survival.”
Read more about the approval of trastuzumab plus pertuzumab in China on OncoDaily: Daiichi Sankyo and AstraZeneca’s trastuzumab Plus Pertuzumab Approved in China for First-Line HER2+ Metastatic Breast Cancer
Trastuzumab’s Expanding Global Reach
Trastuzumab is a HER2-directed DXd antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca.
Trastuzumab plus pertuzumab is now approved in more than 40 countries and regions worldwide as a first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer based on DESTINY-Breast09.
AstraZeneca and Daiichi Sankyo entered their global collaboration to jointly develop and commercialize trastuzumab in March 2019, except in Japan, where Daiichi Sankyo retains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supplying the medicine.
Following the EU approval, AstraZeneca will pay Daiichi Sankyo a $100 million milestone payment for the first-line unresectable or metastatic HER2-positive breast cancer indication. Sales of trastuzumab in most EU territories are recognized by Daiichi Sankyo.
Read further on OncoDaily: European Commission has Granted Marketing Authorization for Gilead Sciences’ Trodelvy Plus Keytruda for First-Line PD-L1-Positive Metastatic TNBC
