fulvestrant

P2, N=17, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Mar 2026

P2, N=51, Not yet recruiting, Novartis Pharmaceuticals

We discuss the case literature on the management of ophthalmic and eyelid metastases, including the role of radiotherapy. We outline the multi-disciplinary team (MDT) discussions and recommendations made in the present case, which ultimately found that the risks of radiation toxicity would outweigh the benefits. Adjuvant therapy with fulvestrant and palbociclib was recommended, with future consideration of a CDK 4/6 inhibitor in the event of metastatic recurrence.

In general, both AI and FUL combinations are effective alternatives, irrespective of the CDK4/6i treatment line, liver metastasis at first relapse, or endocrine sensitivity. Further studies are expected.

In a therapy-resistant xenograft model, combination treatment reduced Fulv-dependent metastatic burden. These findings establish ACSS2 as a driver of endocrine resistance through nuclear acetyl-CoA provision for epigenetic reprogramming, representing a novel therapeutic target in metastatic breast cancer.

Treatment paradigms have advanced from non-targeted options, such as fulvestrant monotherapy or everolimus-based combinations, to precision medicine strategies, including inhibitors of the PI3K/AKT pathway, oral selective estrogen receptor degraders (SERDs), and novel ER-modulating agents, often guided by biomarkers and molecular surveillance... Early second-line standards, including fulvestrant and alpelisib for PIK3CA-mutated tumors, established the basis for biomarker-guided treatment in hormone receptor-positive, HER2-negative metastatic breast cancer...Elacestrant improved progression-free survival in ESR1-mutated disease in the EMERALD trial, capivasertib plus fulvestrant demonstrated significant benefit in tumors harboring AKT/PIK3CA/PTEN pathway alterations in CAPItello-291, and inavolisib plus palbociclib and fulvestrant achieved both progression-free and overall survival improvement in PIK3CA-mutated patients with early relapse in INAVO120... Post-CDK4/6i management increasingly relies on NGS-guided precision approaches, integrating pathway-specific therapies and ctDNA surveillance to tailor sequencing based on resistance profiles, prior ET response, and tumor heterogeneity. Future investigations into novel ER degraders and multi-targeted combinations hold potential to further optimize algorithms, extend non-chemotherapy options, and enhance survival in HR+/HER2- mBC.

P1, N=30, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

P3, N=61, Terminated, SOLTI Breast Cancer Research Group | N=456 --> 61 | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated; The study was prematurely halted because enrollment was significantly delayed compared with the original projections due to the evolving therapeutic landscape.

Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.

P1, N=22, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=48 --> 22

P2, N=98, Recruiting, Fudan University

P2, N=120, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting