Factors for Consideration When Choosing Among Options for Patients with ET-resistant ER+/HER2- mBC

The discussion focuses on treatment options for patients with metastatic HR+/HER2-low breast cancer who progress on first-line CDK4/6 inhibitor plus aromatase inhibitor therapy without ESR1 or PIK3CA mutations, a less common scenario in the current landscape.

If the patient is deemed still endocrine-sensitive based on the duration of response to prior therapy (e.g. >18 months), the standard approach would be fulvestrant, potentially combined with another agent. Spring mentions the ongoing post-MONARCH phase 3 trial of abemaciclib plus fulvestrant versus fulvestrant alone in this setting, which would have been an ideal study for this patient. Retrospective data suggests some patients respond to abemaciclib after prior CDK4/6 inhibitor exposure.

Bhave notes fulvestrant monotherapy is falling out of favor due to limited PFS of 2.5-3 months post-CDK4/6i, but may still benefit a small subset with bone-only or slowly progressing disease. She often combines fulvestrant with everolimus, starting at a reduced dose if toxicity is a concern. Both discuss the promise of novel oral SERDs and SARMs in combination with other targeted agents in ongoing clinical trials as exciting options for endocrine-sensitive disease in this setting.

Upon further progression with liver metastases concerning for endocrine resistance, both prefer capecitabine as the next line, given its oral route, minimal hair loss, and generally good tolerability with flexible dosing. They highlight the importance of toxicity management strategies like diclofenac gel for hand-foot syndrome to optimize quality of life.

This summary was AI-generated and edited for clarity.