As reported on Stock Titan, the European Commission has approved Enhertu® (trastuzumab deruxtecan) as a treatment for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have exhausted satisfactory treatment options. The decision marks a significant milestone in oncology, making Enhertu the first HER2-directed therapy and the first antibody-drug conjugate (ADC) in the European Union to receive a tumor-agnostic indication.
Developed by Daiichi Sankyo and AstraZeneca, Enhertu is designed to target HER2-expressing cancer cells and deliver a cytotoxic payload directly to tumors. Unlike traditional approvals limited to specific cancer types, this authorization is based on the presence of the HER2 biomarker rather than the tumor’s site of origin.
Approval Supported by Multiple Phase 2 Studies
The EU approval was supported by data from three phase 2 clinical trials—DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02—which evaluated the drug in patients with various HER2-positive cancers.
In the DESTINY-PanTumor02 study, a subgroup of 111 previously treated patients with HER2-positive tumors achieved an objective response rate (ORR) of 52.3%, with a median duration of response (DOR) of 21.1 months. The trial included a range of tumor types, including biliary tract, bladder, cervical, endometrial, ovarian, and pancreatic cancers.
Among patients with HER2-positive non-small cell lung cancer (NSCLC) enrolled in DESTINY-Lung01, the therapy produced an ORR of 52.9%, while responses lasted a median of 6.9 months.
In DESTINY-CRC02, which enrolled patients with HER2-positive colorectal cancer, Enhertu achieved an ORR of 46.9% and a median DOR of 5.5 months.
Expanding Precision Oncology Options
Experts say the approval reflects the growing importance of biomarker-driven treatment strategies in cancer care. HER2 overexpression occurs across multiple malignancies and is often linked to more aggressive disease and poorer outcomes. Until now, HER2-targeted therapies in Europe were largely restricted to certain cancer types, such as breast and gastric cancers.
The new tumor-agnostic indication enables clinicians to consider Enhertu for eligible patients based on HER2 status regardless of where the cancer originated, reinforcing the role of comprehensive molecular testing in treatment selection.
Safety Profile Remains Consistent
Safety findings from the three studies were generally consistent with previous clinical experience involving Enhertu, with no unexpected adverse events reported.
The most frequently observed grade 3 or 4 treatment-related adverse reactions in pooled analyses included:
- Neutropenia (18.5%)
- Anemia (9.9%)
- Fatigue (8.2%)
- Leukopenia (5.8%)
- Thrombocytopenia (5.2%)
- Nausea (4.8%)
- Lymphopenia (4.2%)
- Hypokalemia (3.6%)
- Elevated liver enzymes (3.6%)
Less common but serious events included pneumonia and reduced cardiac ejection fraction. Fatal adverse reactions occurred in approximately 1.1% of treated patients, with interstitial lung disease (ILD)/pneumonitis representing the majority of these cases.
Growing Global Footprint
With this latest authorization, Enhertu now holds six approved indications in the European Union. The agent has already been approved in more than 40 countries and regions for several HER2-positive cancers, including breast, gastric, and lung malignancies.
Regulatory reviews are also continuing in Europe for additional breast cancer indications, including use in combination with pertuzumab as a first-line treatment for metastatic HER2-positive breast cancer and for patients with residual invasive disease following neoadjuvant HER2-targeted therapy.
Outlook
The EU’s approval of Enhertu as a tumor-agnostic therapy represents an important advance in precision oncology. By focusing on HER2 expression rather than tumor location, the decision broadens access to targeted treatment for patients with a variety of difficult-to-treat metastatic cancers and underscores the ongoing shift toward biomarker-based cancer care.
