China's National Medical Products Administration has approved trastuzumab deruxtecan (T-DXd; Enhertu) monotherapy for treating adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2 therapies. Simultaneously, the European Commission approved the antibody-drug conjugate as second-line treatment for HER2-positive advanced gastric cancer, representing significant regulatory milestones for this innovative therapy developed by Daiichi Sankyo and AstraZeneca.
Breakthrough Efficacy in Breast Cancer
The Chinese approval was based on compelling data from the phase 3 DESTINY-Breast03 trial, which enrolled 524 patients treated with either 5.4 mg/kg of T-DXd or trastuzumab emtansine (T-DM1; Kadcyla). The study demonstrated that T-DXd yielded a 72% reduction in the risk of disease progression or death compared with T-DM1 (HR, 0.28; 95% CI, 0.22-0.37; P <.000001).
The progression-free survival results were particularly striking, with median PFS not reached for T-DXd (95% CI, 18.5-not evaluable) compared to 6.8 months (95% CI, 5.6-8.2) with T-DM1. This represents a substantial improvement in disease control for patients with HER2-positive metastatic breast cancer.
"This approval marks an important day for the breast cancer community in China as patients with HER2-positive metastatic breast cancer continue to need additional treatment options," said Binghe Xu, MD, professor and director of the Department of Medical Oncology at Cancer Hospital and Institute Cancer Hospital of the Chinese Academy of Medical Sciences. "Despite initial treatment, patients with HER2-positive metastatic breast cancer will often experience disease progression, demonstrating the importance of early systemic disease control and the potential for T-DXd to help eligible patients with metastatic breast cancer."
European Approval for Gastric Cancer
The European Commission approval on December 19th allows trastuzumab deruxtecan use in combination with chemotherapy (gemcitabine plus cisplatin) for adult patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma previously treated with a trastuzumab-based regimen. This approval was based on results from the DESTINY-Gastric02 and DESTINY-Gastric01 Phase II trials.
Eric Van Cutsem, MD, PhD, Head of the Department of Oncology at the University of Leuven, Belgium, emphasized the clinical significance: "This news is a welcome advance for patients with HER2-positive advanced gastric cancer. Patients with this disease face poor outcomes following progression on initial treatment with a HER2-directed medicine as many do not respond to further treatment, and even those that do respond often do not have durable responses."
Novel Mechanism of Action
Trastuzumab deruxtecan represents the first antibody-drug conjugate approved in Europe for advanced gastric cancer treatment. The therapy combines two active components: trastuzumab, a monoclonal antibody that attaches to HER2 and activates immune system cells to kill cancer cells while stopping HER2 from stimulating cancer cell growth, and deruxtecan, a toxic substance that kills cells during division and growth after the trastuzumab component enters the cancer cell.
Safety Profile
The safety profile of T-DXd in DESTINY-Breast03 yielded no new signals and was comparable with previous clinical trials. The most common adverse effects in the trastuzumab deruxtecan arm included nausea (75.9%), fatigue (49.4%), and vomiting (49.0%).
Market Access Implications
The European Commission approval extends to the 27 member states of the European Union, as well as Iceland, Liechtenstein, and Norway. However, the next step requires each country to make this therapy available through their national healthcare systems, a process that varies significantly from country to country, with some approvals happening within months while others may take several years.
These regulatory approvals represent a major advance in treatment options for patients with HER2-positive cancers, addressing significant unmet medical needs in populations that face poor outcomes after initial therapy progression.
