fulvestrant

P1/2, N=1132, Recruiting, Hoffmann-La Roche | N=792 --> 1132

P1, N=30, Not yet recruiting, Northwestern University | N=75 --> 30

P1, N=160, Recruiting, IDEAYA Biosciences | Phase classification: P1/2 --> P1

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Jun 2027

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes...Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients with both early and metastatic HR+, HER2- breast cancer.

P1, N=15, Recruiting, Atridia Pty Ltd. | Not yet recruiting --> Recruiting

P2, N=37, Active, not recruiting, University of Oklahoma | Recruiting --> Active, not recruiting

Patients were divided into three groups: Group A (n=69, palbociclib 125 mg orally, 3 weeks on/1 week off, plus fulvestrant), Group B (n=72, ribociclib 600 mg orally, 3 weeks on/1 week off, plus fulvestrant), Group C (n=99, abemaciclib 150 mg orally, twice daily, plus fulvestrant). However, neither drug exhibits comprehensive superiority across all endpoints. Therefore, clinical treatment decisions should take consideration of multiple factors based on individualized medicine protocol.

PROTACs, especially ER degraders, suggest a potential strategy for addressing endocrine resistance in advanced ER + breast cancer, as reflected in encouraging preliminary clinical data. This integrated analysis highlights the rapid translation of this technology while underscoring the critical need to expand target scope, address inherent resistance mechanisms, and broaden applications to other breast cancer subtypes. Our article synthesizes current knowledge and trial landscape, thereby providing a consolidated foundation to inform future research and clinical development of PROTACs in breast cancer.

P1, N=33, Completed, BeOne Medicines | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Apr 2026

In BCs with alterations in the AKT/PIK3CA pathway, capivasertib, alpelisib, and inavolisib have recently improved progression-free survival (PFS). Inavolisib (GC0077) differs from the other drugs targeting this pathway by its high potency and tolerability when combined with endocrine therapy, mostly with fulvestrant, and a CDK4/6 inhibitor. Its recent use in the first-line combined treatment for advanced HR+/HER2-negative BC has shown a PFS benefit compared to placebo in the INAVO120 trial, suggesting its role as a valid treatment option in PIK3CA-mutated patients. Further studies are warranted to confirm these results in terms of prolonging efficacy and maintaining durable responses - with a manageable safety profile - in clinical practice.

This case represents a rare report of surgical resection for breast cancer liver metastasis after CDK4/6 inhibitor-based therapy. It suggests that local treatment may be effective even in cases with suspected endocrine-resistant disease and provides practical insight into patient selection and treatment strategies, as the case fulfilled previously reported criteria for local therapy.