Early Treatment Switch Strategies for Advanced Breast Cancer

This trial explores whether switching breast cancer treatments earlier, based on molecular signs of disease progression, can better control metastatic breast cancer compared to waiting for standard imaging results. It targets patients with advanced hormone receptor-positive breast cancer and tests various treatment combinations, including hormone therapies and chemotherapy. Those with estrogen receptor-positive, HER2-negative metastatic breast cancer who haven't received prior systemic treatment for advanced disease might be suitable candidates. Participants will have their treatment adjusted when specific molecular changes are detected, rather than waiting for other signs of disease progression. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

The trial does not specify if you need to stop taking your current medications. However, you cannot have had prior systemic anticancer therapy for metastatic or advanced disease, and you should not be on medications that are known to be cytochrome (CYP) 3A4 inhibitors or inducers within 7 days before starting the trial.

Previous studies have shown varying safety levels for the treatments being explored. Research indicates that AI+CDK4/6i combinations are generally safe and well-tolerated, with manageable side effects, though some patients might experience fatigue or low blood counts.

SERD+CDK4/6i treatments are also widely used and considered safe, causing similar side effects like nausea and fatigue, which are usually manageable.

mTOR inhibitor combinations, such as mTOR inhibitor with AI or a selective estrogen receptor modulator, have improved patient outcomes. However, they can cause side effects like mouth sores and high blood sugar, requiring careful management.

Studies show that PI3K inhibitors combined with AI or SERD can effectively control cancer for longer periods. They can, however, cause side effects like high blood sugar and rash, which need monitoring.

Chemotherapy, a more aggressive treatment, is known for causing side effects such as hair loss and nausea. While effective, it can be hard on the body.

Researchers are excited about these treatments for advanced breast cancer because they explore early treatment switch strategies that are not part of the standard care. Unlike typical treatments that stick to one plan until progression, this trial investigates changing therapies early based on molecular changes, like ctDNA levels. This approach could potentially tailor treatments more precisely to individual needs, leading to better outcomes. Additionally, the trial includes a diverse range of drug combinations, such as mTOR and PI3K inhibitors, which offer new mechanisms of action compared to traditional hormone therapies and chemotherapies. By testing these innovative combinations, researchers aim to improve the effectiveness and personalization of breast cancer treatment.

This trial will explore various treatment strategies for advanced breast cancer. Research shows that combining Aromatase Inhibitors (AIs) with CDK4/6 inhibitors can effectively help patients with advanced breast cancer. Participants in this trial may receive AI+CDK4/6i as part of their treatment. Studies have found no major differences in survival rates among the different CDK4/6 inhibitors when used with AIs. Another treatment option in this trial involves using SERDs (Selective Estrogen Receptor Degraders) with CDK4/6 inhibitors, which also shows promise for improving treatment results. When mTOR inhibitors are used with AIs or SERDs, research has shown a significant improvement in progression-free survival, meaning the cancer does not worsen during and after treatment. PI3K inhibitors combined with AIs or SERDs greatly improve progression-free survival and overall response rates in patients with advanced breast cancer. Chemotherapy remains a common treatment, typically offering about two more years of life for those with advanced cases. Participants in this trial may receive these various combinations as part of different treatment arms.¹²³⁴⁶