Hormone Receptor-Positive Metastatic Breast Cancer: Novel Endocrine-Based Strategies and Options After Progression Authors: Volkmar Müller, MD; Erica L. Mayer, MD, MPH

https://www.medscape.org/viewarticle/1002835?sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity Hormone Receptor-Positive Metastatic Breast Cancer: Novel Endocrine-Based Strategies and Options After Progression Below are some key learning points to help reinforce the impact of this activity. ☑ Endocrine therapy (ET) plus a cyclin-dependent kinase (CDK) 4/6 inhibitor is considered the standard of care in the first-line setting for hormone receptor (HR)-positive/HER2-negative metastatic breast cancer. However, resistance is common and subsequent sequential monotherapy ET is associated with a low progression-free survival (PFS). ☑ New strategies are being explored for different populations among HR+/HER2-negative metastatic breast cancer patients to optimize time on therapy, with some phase 3 trials reported: • INAVO120: first-line inavolisib vs placebo (both + palbociclib–fulvestrant) in patients with PIK3CA-mutated disease and recurrence during or within 12 months after adjuvant ET. Median PFS was 17.2 vs 7.3 months, highlighting importance of baseline tumor genomic profiling to identify targetable mutations such as PIK3CA. • SERENA-6: switch from aromatase inhibitor (AI) to camizestrant, continuing a CDK4/6 inhibitor, upon detection of ESR1 mutation and no evidence of disease progression. Median PFS was 16.0 vs 9.2 months, providing further validation of a serial monitoring approach for ESR1 mutation during first-line treatment to prolong PFS. • VERITAC-2: novel proteolysis-targeting chimera (PROTAC) vepdegestrant vs fulvestrant following disease progression. Median PFS was 5.0 vs 2.0 months in the ESR1-mutated population, providing efficacy evidence for this new class of agents.