The HER2-targeted treatment combination has been approved as a new treatment option aimed at delaying disease progression in HER2-positive advanced breast cancer.
Developments in breast cancer treatment in recent years have led to significant improvements in patients' survival and quality of life, particularly through therapies targeting the biological characteristics of tumors. One of the recent developments in this field has been the expansion of treatment options for HER2-positive, unresectable locally advanced or metastatic breast cancer.
On October 7, 2026, the U.S. Food and Drug Administration (FDA) approved the use of a HER2-targeted treatment combination as maintenance therapy in adult patients whose disease had not progressed following initial treatment. This decision introduces a new approach aimed at maintaining disease control for a longer period in HER2-positive metastatic breast cancer.
What Is HER2-Positive Breast Cancer?
HER2 is a protein involved in the growth and proliferation of cells. In some breast cancers, this protein is present at higher-than-normal levels, or an increase in the HER2 gene is detected. This condition may cause tumor cells to multiply more rapidly.
However, HER2-positive breast cancer is also a group of diseases that can benefit significantly from targeted therapies. Drugs targeting HER2 play an essential role in the treatment of this disease.
When the disease spreads to distant organs, it is referred to as metastatic breast cancer. At this stage, the main goals of treatment are to delay disease progression, control symptoms, maintain quality of life, and extend survival as much as possible.
How Does the New Treatment Combination Work?
The combination approved by the FDA consists of three drugs:
- An orally administered targeted tyrosine kinase inhibitor that blocks HER2 signaling inside the cell.
- A monoclonal antibody that targets the HER2 protein.
- A monoclonal antibody that blocks HER2 signaling through a different mechanism.
The combined use of these three drugs suppresses the HER2 signaling pathway at different points. The aim is to delay further disease progression in patients who have responded to initial treatment.
One of the important features of this approach is that it offers the option of continuing HER2-targeted therapy without continuing chemotherapy during the maintenance phase. However, the patient's previous treatments, tumor characteristics, and overall health status are determining factors in treatment decisions.
What Do the Clinical Trial Results Show?
The new approval is based on the results of a phase 3 clinical trial called HER2CLIMB-05. The study included 654 adult patients whose disease had not progressed following initial treatment.
After receiving HER2-targeted drugs and taxane-based chemotherapy as initial treatment, the patients were divided into two groups. One group received the investigational targeted drug together with standard HER2-targeted therapy, while the other group received a placebo together with standard HER2-targeted therapy.
The main results of the study were as follows:
- Median progression-free survival was 24.9 months in the group receiving the additional investigational drug.
- Median progression-free survival was 16.3 months in the comparison group.
- The difference in median progression-free survival between the two groups was 8.6 months.
- An approximately 36% relative reduction in the risk of disease progression or death was observed.
These results show that adding the investigational drug to existing HER2-targeted maintenance therapy could significantly delay disease progression in the patient population included in the study.
However, progression-free survival and overall survival are not the same concepts. Progression-free survival refers to the period during treatment in which the disease does not progress. At the time of the FDA approval assessment, the overall survival data were not yet mature. Therefore, longer-term follow-up results are needed to determine the effect of the new combination on overall survival.
Patient Population Covered by the FDA Approval
The new treatment option is not automatically suitable for every patient with HER2-positive breast cancer. The FDA approval specifically covers adult patients with the following characteristics:
- Patients with unresectable locally advanced or metastatic HER2-positive breast cancer,
- Patients who have received HER2-targeted drugs and taxane-based chemotherapy as initial treatment,
- Patients whose disease has not progressed following initial treatment.
Patients with brain metastases were also included in the study. However, this does not mean that all patients with brain metastases will benefit equally from the same treatment. The status of the disease in the brain, previous treatments, and other clinical characteristics must also be evaluated.
In patients with hormone receptor-positive disease, endocrine therapy may also be continued when considered appropriate.
Treatment Side Effects and Monitoring
Although targeted therapies aim to suppress cancer cells through specific molecular mechanisms, they also carry a risk of side effects. In the investigated targeted treatment combination, careful monitoring is particularly necessary for liver function and diarrhea.
The most commonly reported side effects include diarrhea, nausea, vomiting, fatigue, rash, and musculoskeletal pain. Liver injury can be serious and, in rare cases, life-threatening. Therefore, liver function tests should be performed regularly before and throughout treatment.
When dose adjustments, treatment interruptions, or treatment discontinuation are necessary, the decision should be made by the physician based on the patient's clinical condition and the severity of side effects.
What Does This Development Mean for Breast Cancer Treatment?
The success of treatment in metastatic breast cancer is not measured solely by the response to initial treatment. How long the achieved response can be maintained is also of great importance. Therefore, maintenance therapies aimed at sustaining disease control after initial treatment are among the important components of modern oncology.
The new FDA approval concerning the HER2-targeted treatment combination expands the treatment options for HER2-positive metastatic breast cancer. The increase in progression-free survival from 16.3 months to 24.9 months in the study was evaluated in terms of the duration of disease control in the patient population included in the research.
However, treatment selection should be based on a combined assessment of the tumor's biological characteristics, the patient's previous treatments, accompanying diseases, risk of side effects, and patient expectations.
An important point regarding Türkiye is that FDA approval means the treatment has been authorized for the specified use in the United States. Its regulatory approval status, availability, and reimbursement conditions in Türkiye must be evaluated separately.
Treatment options for HER2-positive metastatic breast cancer continue to evolve. The new HER2-targeted combination is being investigated for its potential to delay disease progression through a chemotherapy-free maintenance approach in eligible patients.
Integrating current scientific evidence into clinical practice, planning treatment according to each patient's individual characteristics, and multidisciplinary evaluation form the foundation of breast cancer management.
