Clinical Trial Comparing Trastuzumab Deruxtecan to Standard Therapy in Early-Stage HER2-Positive Breast Cancer (Neoadjuvant)

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue characterized by the uncontrolled proliferation of breast gland cells. In its early stages, the disease is confined to the breast. As the disease progresses, it often spreads to the lymph nodes and forms secondary tumors (metastases) in other parts of the body (bones/organs). This is referred to as metastatic disease, which corresponds to stage 4.

Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the tumor growth rate (Ki-67 index), detectable hormone receptors (HR) on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of HER2 receptors on the cells (HER2-positive). Treatment for breast cancer at a locally confined stage with no evidence of metastases typically involves breast-conserving surgery preceded by chemotherapy (neoadjuvant), with the goal of complete recovery. To reduce the risk of the disease returning, radiation therapy and drug therapy (adjuvant) may be administered after surgery. The more risk factors there are for a recurrence of the disease, the more important this treatment becomes. In HER2-positive cases, this therapy specifically targets the HER2 surface receptor on the tumor cells. Trastuzumab deruxtecan is an antibody-drug conjugate that specifically binds to the HER2 receptor and delivers the chemotherapeutic agent (deruxtecan) directly to the cells. This enhances the drug’s effectiveness while ensuring that only the breast cancer cells are targeted. The drug is already approved for the treatment of recurrent HER2-positive breast cancer.

The goal of this Phase 2 study is to investigate the efficacy and safety of neoadjuvant therapy with trastuzumab deruxtecan and to compare it with the current standard of care (chemotherapy). Based on tumor characteristics, patients are first assigned to either a low/intermediate-risk group or a high-risk group according to specific risk factors associated with the disease. Participants are then randomly assigned to one of two groups within their respective risk group. Group 1 (study arm) receives neoadjuvant therapy with trastuzumab deruxtecan for 12 weeks (low/intermediate risk) or 18 weeks (high risk). Group 2 (control arm) receives standard treatment with paclitaxel, trastuzumab, and pertuzumab for 12 weeks (low/intermediate risk) or docetaxel/paclitaxel, carboplatin, trastuzumab, and pertuzumab for 18 weeks (high-risk group). Depending on the response to therapy, the corresponding medication may be continued for one year after surgery. The study is not blinded, meaning that both the medical staff and the patient know which medications are being administered. Treatments and follow-up examinations as part of the study will continue for up to 3.5 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease recurs during treatment.

Patients aged 18 and older, whether premenopausal or postmenopausal, with locally advanced breast cancer are eligible to participate in this study. The disease must be untreated and HER2-positive.