Dr. Kelly McCann reviews sequencing and emerging therapies in HR-positive, HER2-negative metastatic breast cancer. Top research highlights from ESMO Breast Cancer 2025 showcase advances in treatment and care for patients with breast cancer. New drugs like vepdegestrant and oral SERDs may reshape HR+ breast cancer treatment with novel mechanisms and CDK4/6 combos. Dr. Sammons on RLY-2608 plus fulvestrant in HR+/HER2– mBC with PIK3CA mutations: safety, efficacy, and trial updates. INAVO120 shows OS benefit with inavolisib in PIK3CA-mutated HR+/HER2– aBC, raising new considerations for first-line care. ADELA trial explores elacestrant + everolimus for ESR1-mutated breast cancer post-CDK4/6, aiming to boost 2L outcomes.
Vepdegestrant improves PFS in ESR1-mutant ER+/HER2- breast cancer, offering a well-tolerated oral option post-CDK4/6. Stephanie Graff, MD, reviews top ASCO25 breast cancer trials, including ASCENT-04, DESTINY-Breast09, and SERENA-6.
Elinzanetant reduces vasomotor symptoms from endocrine therapy in HR+ breast cancer, with rapid onset and good tolerability. AI-powered TIL analysis may predict pCR and survival outcomes in HR+/HER2– breast cancer treated with neoadjuvant chemo. About 1 in 10 patients with high RS early HR+/HER2- BC decline chemo, which is tied to worse overall survival, per ASCO data. Imlunestrant improved quality of life and physical function in patients with ER+/HER2– breast cancer in the EMBER-3 trial. Inavolisib + palbociclib + fulvestrant extends OS and delays chemo in PIK3CA-mutant HR+/HER2- advanced breast cancer. Imlunestrant plus abemaciclib improved PFS across subgroups in ER+/HER2- breast cancer, per EMBER-3 data. Abemaciclib plus fulvestrant showed benefit across biomarkers after CDK4/6i failure in advanced HR+/HER2- breast cancer. About 40% of patients on AI + palbociclib developed ESR1 mutations in PADA-1, emerging as early as 6 months into treatment. Dual immunotherapy plus trastuzumab shows activity in ER+ or PD-L1+ trastuzumab-resistant HER2+ breast cancer. T-DXd improved PFS and response rates vs chemo in HR+/HER2-low or -ultralow metastatic breast cancer in DESTINY-Breast06. Ribociclib plus ET shows similar pCR rates to chemo in intermediate-risk HR+/HER2– early breast cancer, per WSG ADAPTcycle. PALMIRA trial shows limited benefit of palbociclib rechallenge in HR+/HER2- breast cancer, guiding future treatment choices.