Enhertu (trastuzumab deruxtecan): CHMP opinion on variation to marketing authorisation in HR-positive HER2-low or -ultralow breast cancer
On 27 February 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Enhertu (trastuzumab deruxtecan). The marketing authorisation holder for this medicinal product is Daiichi Sankyo Europe GmbH.
The CHMP adopted an extension to an existing indication to include treatment of adults with unresectable or metastatic HR-positive HER2-low or -ultralow breast cancer (2L+ chemo-naïve HR+/HER2-low/ultralow mBC after prior ET).
The full indications for Enhertu will therefore be as follows (in bold the new extension):
Breast cancer
HER2-positive breast cancer
Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.
HER2-low and HER2-ultralow breast cancer
Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic
- hormone receptor (HR)-positive, HER2-low or HER2-ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment.
- HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy (see section 4.2).
Non-small cell lung cancer (NSCLC)
Enhertu as monotherapy is indicated for the treatment of adult patients with advanced NSCLC whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.
Gastric cancer
Enhertu as monotherapy is indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
The positive opinion is supported by results from the Phase 3 DESTINY-Breast06 clinical trial, which was presented at ASCO 2024 and published in The New England Journal of Medicine
T-DXd significantly improved PFS vs TPC in HER2-low patients (HR: 0.62; median PFS: 13.2 vs 8.1 mo); ITT results (HER2-low and ultralow) were numerically consistent with the HER2-low group (HR:0.64)
Based on the CHMP timetable, T-DXd is likely to be granted market authorization by the European Commission (EC) by May 2025 (~67 days from positive opinion)
Source: CHMP post-authorisation summary of positive opinion for Enhertu (II-48)