Enhertu Gains EU Approval for Previously Treated HER2-Positive Solid Tumours
AstraZeneca and Daiichi Sankyo have announced that the European Commission (EC) has approved Enhertu® (trastuzumab deruxtecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumours who have previously received treatment and have no satisfactory therapeutic options remaining. The approval marks a major advancement in precision oncology by introducing the first tumour-agnostic indication in the European Union (EU) for a HER2-directed therapy and antibody-drug conjugate (ADC).
The decision significantly expands the availability of Enhertu beyond its existing tumour-specific indications, enabling physicians to prescribe the therapy based on the molecular characteristics of a patient’s cancer rather than the organ in which the tumour originated. The milestone reinforces the growing role of biomarker-driven medicine in oncology and provides a new treatment option for patients with advanced HER2-positive cancers who previously had limited alternatives.
A Landmark Approval in Precision Oncology
The European Commission’s authorization follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The approval is based on compelling clinical evidence demonstrating the activity of Enhertu across several HER2-positive tumour types, regardless of their anatomical origin.
Unlike traditional cancer treatments that are approved for cancers arising in a specific organ, tumour-agnostic therapies target a shared molecular alteration found across multiple malignancies. In this case, the approval focuses on tumours that exhibit HER2 overexpression (IHC 3+), allowing eligible patients from several cancer types to receive the same targeted therapy.
The decision reflects a broader shift toward precision medicine, where treatment selection increasingly depends on genomic and molecular testing rather than tumour location alone.
Addressing an Important Unmet Medical Need
HER2 overexpression is present across numerous solid tumours, although its prevalence varies among different cancer types. Patients whose tumours overexpress HER2 often experience more aggressive disease and poorer clinical outcomes.
Historically, HER2-targeted therapies have primarily been available for breast, gastric, and selected lung cancers. Patients with HER2-positive disease arising in other organs frequently lacked approved targeted treatment options despite sharing the same molecular driver.
The new approval helps address this gap by extending access to HER2-directed therapy for patients with advanced cancers who have exhausted available standard treatments.
Because the indication is tumour agnostic, clinicians can now consider Enhertu for eligible patients based on HER2 testing results, regardless of where the cancer originated.
Clinical Expert Highlights Significance
Benedikt Westphalen, MD, Head of the Precision Oncology Program at the Comprehensive Cancer Center of the University of Munich, emphasized the importance of the approval for patients and healthcare providers.
He explained that HER2 overexpression occurs across multiple tumour types and is generally associated with aggressive disease biology and an unfavorable prognosis.
Until now, treatment options specifically targeting HER2 were largely limited to selected tumour types. According to Westphalen, the approval of trastuzumab deruxtecan as a tumour-agnostic therapy creates an entirely new therapeutic opportunity for patients with HER2-positive cancers regardless of the tissue or organ in which the malignancy developed.
He noted that the decision represents another important step toward implementing molecularly guided cancer care across Europe.
AstraZeneca Highlights Growing Role of Biomarker Testing
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval reflects the continued transformation of cancer treatment through precision medicine.
He noted that molecular testing increasingly enables physicians to select therapies based on the biological characteristics of each patient’s disease rather than relying solely on tumour location.
Fredrickson explained that Enhertu is already approved in Europe for several tumour-specific indications, including breast, gastric, and lung cancers.
With the addition of this tumour-agnostic indication, physicians now have the opportunity to consider Enhertu for patients with HER2-positive disease across a much broader range of advanced solid tumours.
He also emphasized the growing importance of routine biomarker testing, which helps identify patients eligible for targeted therapies and supports more personalized treatment decisions.
Daiichi Sankyo Marks Major Regulatory Milestone
Ken Keller, Global Head of Oncology Business and President and Chief Executive Officer of Daiichi Sankyo, described the approval as a significant achievement for both patients and the companies’ oncology collaboration.
According to Keller, the authorization establishes the first HER2-directed antibody-drug conjugate with a tumour-agnostic indication in the European Union.
He noted that Enhertu is now approved for six separate indications within the EU, demonstrating the companies’ ongoing commitment to expanding treatment options for patients with difficult-to-treat cancers.
The approval further strengthens the global clinical development program surrounding Enhertu and reflects years of investment in advancing targeted oncology therapies.
Clinical Data Supporting the Approval
The European Commission based its decision on efficacy data from patients with HER2-positive (IHC 3+) tumours enrolled across three Phase II clinical trials:
- DESTINY-PanTumor02
- DESTINY-Lung01
- DESTINY-CRC02
Together, these studies evaluated the effectiveness of Enhertu in several advanced solid tumours that had progressed despite previous treatment.
The results consistently demonstrated meaningful anti-tumour activity across multiple cancer types.
DESTINY-PanTumor02 Results
The DESTINY-PanTumor02 Phase II study evaluated patients with previously treated HER2-positive (IHC 3+) advanced solid tumours.
The study included several tumour types, including:
- Biliary tract cancer
- Bladder cancer
- Cervical cancer
- Endometrial cancer
- Ovarian cancer
- Pancreatic cancer
- Other HER2-positive solid tumours
Among 111 patients, Enhertu achieved a confirmed objective response rate (ORR) of 52.3%.
The therapy also demonstrated a median duration of response (DOR) of 21.1 months, indicating that many responding patients experienced durable clinical benefit.
These findings suggest that more than half of treated patients experienced meaningful tumour shrinkage despite having advanced disease and limited remaining treatment options.
DESTINY-Lung01 Findings
The DESTINY-Lung01 Phase II trial evaluated patients with previously treated HER2-positive (IHC 3+) non-small cell lung cancer (NSCLC).
Among 17 evaluable patients, Enhertu produced:
- Confirmed objective response rate: 52.9%
- Median duration of response: 6.9 months
Although the study population was relatively small, the results demonstrated substantial anti-tumour activity in this difficult-to-treat patient group.
DESTINY-CRC02 Results
The DESTINY-CRC02 Phase II study focused on patients with HER2-positive metastatic colorectal cancer.
Among 64 patients, investigators observed:
- Confirmed objective response rate: 46.9%
- Median duration of response: 5.5 months
These outcomes further supported the consistency of Enhertu’s activity across multiple HER2-positive malignancies.
Consistent Safety Profile
The safety evaluation supporting the approval incorporated pooled data from patients enrolled in:
- DESTINY-PanTumor02
- DESTINY-Lung01
- DESTINY-CRC02
- DESTINY-Breast01
According to AstraZeneca and Daiichi Sankyo, the pooled analysis demonstrated a safety profile consistent with previous clinical experience.
Importantly, investigators reported no new safety concerns, and the adverse event profile aligned with that observed in earlier studies of Enhertu across its approved indications.
The consistency of the safety findings provides additional confidence regarding the therapy’s benefit-risk profile across diverse tumour types.
Expanding Global Regulatory Success
The European Union joins several other regions that have already granted tumour-agnostic approval for Enhertu.
The therapy has previously received tumour-agnostic authorization in the United States and other international markets based on the same body of evidence generated through the DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 studies.
The expanding list of regulatory approvals reflects growing international recognition of HER2 as an actionable biomarker across multiple advanced cancers.
Ongoing Regulatory Reviews
Beyond the newly approved tumour-agnostic indication, AstraZeneca and Daiichi Sankyo continue pursuing additional regulatory approvals for Enhertu in Europe.
Applications currently under review include:
- Enhertu in combination with pertuzumab as first-line therapy for patients with unresectable or metastatic HER2-positive breast cancer based on the Phase III DESTINY-Breast09 trial.
- Enhertu for patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant HER2-targeted therapy based on results from the Phase III DESTINY-Breast05 study.
These ongoing submissions reflect the companies’ strategy to further expand the clinical role of Enhertu across earlier stages of breast cancer treatment.
About Enhertu
Enhertu is a specifically engineered HER2-directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo.
The therapy combines a HER2-targeting monoclonal antibody with a potent topoisomerase I inhibitor payload through a specialized linker technology designed to selectively deliver chemotherapy to HER2-expressing tumour cells while limiting exposure to surrounding healthy tissue.
Enhertu is jointly developed and commercialized worldwide through a strategic collaboration between AstraZeneca and Daiichi Sankyo.
Since its initial approvals, the therapy has become an important treatment option across multiple HER2-positive cancers and continues to be evaluated in an extensive global clinical development program.
Financial Impact of the Approval
The European Commission’s approval also triggers a financial milestone under the collaboration agreement between AstraZeneca and Daiichi Sankyo.
Following the authorization, AstraZeneca will make a $25 million milestone payment to Daiichi Sankyo related to the tumour-agnostic indication.
Under the companies’ existing collaboration agreement established in March 2019, Daiichi Sankyo recognizes sales of Enhertu across most European Union markets.
The partnership continues to represent one of the largest oncology collaborations in the industry, supporting the global development and commercialization of Enhertu across an expanding range of cancer indications.
The European Commission’s approval of Enhertu for previously treated adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumours marks a major advancement in precision oncology. As the first HER2-directed antibody-drug conjugate approved with a tumour-agnostic indication in the European Union, the therapy expands access to targeted treatment for patients whose cancers share a common molecular characteristic rather than a common tissue of origin.
Supported by strong efficacy data across multiple Phase II studies and a well-established safety profile, the approval reinforces the growing importance of biomarker testing in guiding cancer treatment decisions. With additional regulatory applications under review and an expanding clinical development program, AstraZeneca and Daiichi Sankyo continue working to broaden the role of Enhertu across multiple cancer settings, further advancing the promise of personalized medicine for patients with difficult-to-treat HER2-positive malignancies.
