Kisqali (ribociclib)

Treatment durations, discontinuation rates, and subsequent treatments differ between CDK4/6is for HR+/HER2- mBC in US routine clinical practice.

Furthermore, this combination therapy remodels the bone niche to significantly enhance the efficacy of adoptive T cell immunotherapy. Collectively, these results suggest that the synergy between CDK4/6i and doxorubicin represents a promising therapeutic strategy to overcome the protective signals of the bone microenvironment in metastatic breast cancer.

This study provides relevant local evidence and supports its use in real-world settings. Longer follow-up is needed to more accurately assess OS and PFS outcomes.

P=N/A, N=175, Completed, Novartis Pharmaceuticals | Recruiting --> Completed | N=550 --> 175

Our findings demonstrate that ZR interacting proteins constitute therapeutic leads, and that XPO1 is critical for titrating 'goldilocks' levels of ZR nuclear expression. We identify a novel combination therapy of Selinexor, Gemcitabine, and Ribociclib that may be immediately translated into clinical trials for EPN patients that are currently without targeted treatments.

The introduction of selective CDK4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, in combination with endocrine therapy, has significantly improved clinical outcomes and has become a standard treatment strategy in both metastatic and high-risk early-stage disease. Particular attention is given to the application of in silico approaches, including molecular docking, molecular dynamics simulations, and binding free-energy calculations, which provide insights into mechanisms of therapy resistance and potential strategies to overcome them and support the identification and optimization of novel CDK4/6-targeted therapeutic candidates. By integrating structural, clinical, and computational perspectives, this review highlights current knowledge and emerging directions in CDK4/6 research that may advance the development of more personalized therapies for HR+/HER2- breast cancer, while accounting for both intrinsic and de novo resistance mechanisms.

In contrast, monarchE (abemaciclib) and NATALEE (ribociclib) showed significant improvements in iDFS and, in the case of abemaciclib, a signal of benefit in overall survival, supporting the existence of a clinically relevant post-treatment effect. From a biological perspective, the review proposes that the "carry-over" effect should not be considered a uniform class effect, but rather the result of a sequence of events modulated by pharmacological selectivity (CDK4 vs. CDK6 and additional targets), the induction of cellular senescence, and immunomodulatory effects that could favor the control of micrometastases. In addition, elements that influence interpretation and the need to optimize adherence and toxicity management to "materialize" the benefit in a potentially curable context are discussed.

CDK4/6 inhibitors plus endocrine therapy significantly improved survival in hormone receptor-positive, HER2-negative advanced breast cancer. Benefits in progression-free survival and overall survival were consistent across major clinical subgroups. Although all agents improved progression-free survival, only ribociclib and abemaciclib showed statistically significant overall survival benefits, whereas palbociclib did not, and data for dalpiciclib remain immature. Further head-to-head comparisons and assessments of toxicity profiles, as well as patient-reported outcomes, are needed.

P2, N=94, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University | Not yet recruiting --> Recruiting

P1/2, N=792, Recruiting, Hoffmann-La Roche | N=56 --> 792

P1, N=241, Recruiting, Totus Medicines | N=175 --> 241

P4, N=46, Recruiting, Pfizer | N=71 --> 46