Ibrance (palbociclib)

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

mRNA sequencing reveals an FASTIS-associated transcriptomic profile that overlaps between ACC and FASN inhibitors yet differs significantly from that of other mechanistically diverse TIS inducers, including bleomycin, alisertib, doxorubicin, and palbociclib. The FASTIS phenomenon is a therapeutic outcome through which cancer cells adapt to survive clinical-grade lipogenesis inhibitors. The cholesterol-addicted FASTIS fate can be rationally exploited as a collateral sensitivity in "one-two punch" senogenic-(immuno)senolytic strategies.

A transcriptional signature associated with SARM sensitivity was identified, primarily driven by proliferation-related processes, consistent with a significant decrease in S-phase cell cycle proteins upon treatment in EP0062-sensitive models. In some EP0062-resistant tumors, the combination with palbociclib enhanced the antitumor effect of EP0062, suggesting a potential strategy for metastatic patients with acquired ET resistance.

We retrospectively analyzed 332 patients with hormone receptor-positive/HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between 2018 and 2023. These findings suggest a potential association between BMI and clinical outcomes in this treatment setting. Prospective studies that integrate body composition and pharmacokinetics are required for validation.

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.

Six cycles of systemic chemotherapy with epirubicin and cyclophosphamide at three-week intervals were administered, followed by endocrine therapy with letrozole. Almost four years later, palbociclib became available and it was added to the patient's treatment...As this is a single-case clinical observation, any conclusions have limited generalizability. Given the rarity of primary metastatic ulcerative breast cancer there are no specific evidence-based treatment guidelines available and published studies have high heterogeneity and low level of evidence, necessitating multidisciplinary approach on a case-by-case basis.

P1/2, N=435, Active, not recruiting, Stemline Therapeutics, Inc. | Recruiting --> Active, not recruiting

PADMA is the first randomized multicenter study to show that palbociclib + ET as first-line treatment compared with CT also leads to improvements in TTF and PFS in predominantly postmenopausal patients with HR-positive/HER2-negative mBC.

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.

P=N/A, N=68, Active, not recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028

The majority of patients (72%) were treated in the first-line setting; 11 received ribociclib, 15 received palbociclib, and 3 received abemaciclib. Whether this translates into deferring disease progression requires randomized studies with larger treatment groups. To our knowledge, this study represents the first analysis evaluating 18F-FDG-PET/CT-guided SBRT in combination with CDK4/6 inhibitor-based therapy in patients with metastatic breast cancer.

Palbociclib, ribociclib, and abemaciclib, which are FDA-approved CDK4/6 inhibitors, constitute the standard first-line treatment for advanced hormone receptor-positive (HR+) breast cancers. Collectively, this study deepens the understanding of shared and drug-specific molecular characteristics and mechanisms of CDK4/6 inhibitors at multi-omic levels. Moreover, it provides an experimental basis and potential directions for customizing combination therapies based on pathway vulnerabilities, as well as exploration of novel therapeutic modes and drugs.