Radiation + HER2-targeted Therapy for Leptomeningeal Metastasis from Breast Cancer

This trial explores whether combining radiation therapy with two medications, trastuzumab and pertuzumab, can safely improve survival for individuals with HER2-positive breast cancer that has spread to the leptomeninges, the protective layers around the brain and spinal cord. Participants will first receive radiation, followed by varying doses of the medications to determine the safest and most effective treatment plan. This trial may suit those diagnosed with HER2-positive breast cancer that has spread to the brain or spinal fluid and who are willing to undergo specific procedures like Ommaya reservoir placement, a small device used for delivering medication directly to the brain. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

You may need to stop taking certain medications, especially those that affect the central nervous system, unless your condition worsened while on them. However, you can continue with some HER2-targeted therapies if they are controlling your disease.

Studies have shown that trastuzumab and pertuzumab, when combined with chemotherapy, improve survival rates in patients. Research indicates that administering trastuzumab directly into the spinal fluid is well-tolerated and may enhance overall survival for patients with HER2-positive breast cancer. However, this study remains in its early stages, focusing on the safety of these treatments when combined with radiation. Although these treatments are approved for other uses, the current study aims to provide more specific safety data for this combination in treating breast cancer that has spread to the membranes around the brain and spinal cord.¹²³⁴⁵

Researchers are excited about these treatments for leptomeningeal metastasis from breast cancer because they combine radiation therapy with a targeted approach using pertuzumab and trastuzumab. Unlike standard treatments, which often involve systemic chemotherapy, this approach directly delivers the drugs via an Ommaya reservoir, potentially improving drug delivery to the brain and spinal cord. Pertuzumab and trastuzumab target the HER2 protein, which is overexpressed in some breast cancers, aiming to more effectively halt cancer growth. The different dosing levels of pertuzumab in the study allow researchers to explore optimal dosages for safety and effectiveness. This targeted method could offer a more precise and potentially less toxic treatment compared to conventional options.

Studies have shown that radiation therapy is an important tool for treating leptomeningeal disease in breast cancer, helping some patients live longer. In this trial, participants will receive radiation therapy followed by varying doses of trastuzumab and pertuzumab. These targeted treatments have shown promise for HER2-positive breast cancer. Administering trastuzumab directly into the spinal fluid has improved or stabilized the condition in many cases. Combining pertuzumab with trastuzumab has led to significant improvements, helping patients live longer and better. Overall, this combination of treatments shows potential for improving outcomes in leptomeningeal metastasis from breast cancer.⁵⁶⁷⁸⁹