European Commission | EMA Drug Approvals | 2026 | iPharmaCenter

Badari Andukuri
2 days ago
4 min read

Enhertu Combination Approved in EU as First New First-Line Option in a Decade for HER2-Positive Metastatic Breast Cancer

The European Commission has approved Enhertu, developed jointly by AstraZeneca and Daiichi Sankyo, in combination with pertuzumab as a first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer.

This marks the first new first-line treatment approach authorized in the European Union for this patient group in more than ten years, based on results from the Phase III DESTINY-Breast09 trial. The decision follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

Trial Results Behind the Approval

In the DESTINY-Breast09 study, combining Enhertu with pertuzumab reduced the risk of disease progression or death by 44% compared with the standard treatment combination of a taxane, trastuzumab, and pertuzumab, often referred to as THP.

This benefit was seen in patients who had not previously received chemotherapy or HER2-targeted therapy for advanced disease, or who had completed HER2-targeted treatment before or after surgery more than six months prior to their advanced or metastatic diagnosis.

Median progression-free survival reached 40.7 months with the Enhertu and pertuzumab combination, compared with 26.9 months for those receiving THP, based on assessment by blinded independent central reviewers. This means patients receiving the newer combination went, on average, more than a year longer without their cancer progressing.

Understanding HER2-Positive Breast Cancer

Breast cancer remains the most commonly diagnosed cancer among women worldwide and the leading cause of cancer-related death in women. In 2024, approximately 2.4 million new cases were diagnosed globally, with more than 690,000 deaths linked to the disease. In Europe alone, roughly 540,000 new cases were diagnosed that year, resulting in over 140,000 deaths.

While early-stage breast cancer often has favorable survival outcomes, the picture changes significantly once the disease becomes metastatic. Only about 30% of patients diagnosed with, or who progress to, metastatic breast cancer are expected to survive five years after diagnosis.

About the DESTINY-Breast09 Trial

DESTINY-Breast09 is a global, multicenter, randomized, open-label Phase III trial that compared Enhertu, given either alone or alongside pertuzumab, with standard THP treatment as a first-line therapy for HER2-positive metastatic breast cancer.

Participants were divided evenly into three groups. One group received Enhertu alone alongside a placebo matched to pertuzumab, a second group received Enhertu combined with pertuzumab, and a third group received standard THP treatment. Patients were grouped based on whether their cancer was metastatic from diagnosis or had progressed from earlier-stage disease, along with their hormone receptor status and PIK3CA mutation status.

European Commission Expands Trodelvy Use in First-Line Metastatic Breast Cancer

The European Commission has approved Gilead Sciences’ Trodelvy, also known as sacituzumab govitecan, in combination with pembrolizumab for adults with previously untreated, unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1 at a combined positive score of 10 or higher.

It makes the Trodelvy and pembrolizumab regimen the first antibody drug conjugate and immunotherapy combination authorized for first-line metastatic triple-negative breast cancer in these markets.

New First-Line Option

The European authorization applies to patients who have not previously received systemic treatment for metastatic disease.

It follows an earlier European approval for Trodelvy used alone in adults with unresectable locally advanced or metastatic triple-negative breast cancer who are not candidates for treatment targeting the PD-1 or PD-L1 pathways.

Together, the two decisions provide Trodelvy-based treatment options across PD-L1 status in the first-line metastatic setting. Patients with PD-L1-positive tumors may receive Trodelvy with pembrolizumab, while eligible patients unable to receive PD-1 or PD-L1 therapy may receive Trodelvy alone.

Phase 3 Trial Showed Longer Disease Control

The approval was supported by results from the Phase 3 ASCENT-04 and KEYNOTE-D19 trial.

The international study compared Trodelvy plus pembrolizumab with physician-selected chemotherapy plus pembrolizumab in patients with previously untreated PD-L1-positive metastatic triple-negative breast cancer.

Median progression-free survival was 11.2 months for patients receiving the Trodelvy combination, compared with 7.8 months for those given chemotherapy and pembrolizumab.

The risk of disease progression or death was 35% lower with Trodelvy plus pembrolizumab.

Gilead described the progression-free survival improvement as both statistically significant and clinically meaningful. Overall survival data remain an important part of the continuing assessment of the regimen.

Triple-Negative Breast Cancer

Triple-negative breast cancer does not express estrogen or progesterone receptors and has limited HER2 expression. Because of these characteristics, many hormone-based and HER2-directed treatments are not suitable for this disease.

The cancer tends to behave more aggressively than several other breast cancer subtypes. It is associated with a greater risk of recurrence and metastatic spread, and it affects younger, premenopausal, Black, and Hispanic women disproportionately.

Approximately 15% of breast cancers are triple-negative. For women with metastatic triple-negative disease, the reported five-year survival rate is about 12%, compared with 28% for women with other forms of metastatic breast cancer.

How Trodelvy Works

Trodelvy is an antibody drug conjugate that targets Trop-2, a protein found on the surface of many cancer cells.

The antibody component guides the medicine toward Trop-2 expressing cells. Once delivered, its payload, SN-38, inhibits topoisomerase I, an enzyme cancer cells need to replicate and survive.

The medicine also has a bystander effect, allowing the payload to affect nearby tumor cells in the surrounding tumor environment. Trop-2 is highly expressed in several cancers, including most breast and lung tumors.

Broader Treatment Implications

The European decision expands the role of Trodelvy earlier in the treatment pathway for metastatic triple-negative breast cancer.

For patients with PD-L1-positive tumors, the combination with pembrolizumab offers an antibody drug conjugate paired with immunotherapy at the start of metastatic treatment. The separate monotherapy approval extends Trodelvy’s reach to patients who are not candidates for PD-1 or PD-L1 inhibitor treatment.

Treatment selection will depend on tumor characteristics, prior therapy, eligibility for immunotherapy, and the clinical judgment of the treating oncology team.