Kisqali (ribociclib)

 Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.

The results of the screen revealed that a PI3K inhibitor, copanlisib, combined with a CDK4/6 inhibitor, ribociclib, exhibited strong synergistic anti-Ewing sarcoma activity. In two xenograft models of Ewing sarcoma, we demonstrated that the combination significantly prolonged survival compared to treatment with either vehicle or single-agent therapy alone. Our findings identify a new candidate therapy combination for Ewing sarcoma and provide a resource of additional potential synergistic combinations for future validation.

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

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.

P3, N=150, Not yet recruiting, AstraZeneca

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.

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

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.

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

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.

P4, N=90, Not yet recruiting, Institute of Oncology Ljubljana