Kisqali (ribociclib)

Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.

We identified FDA-approved compounds acting through these pathways, three of which, Ribociclib, Ponatinib, and Dasatinib, showed superior efficacy to current therapies across renal cancer cell lines in preclinical screens. By acting through mechanisms distinct from current therapies, they represent promising candidates for combination strategies aimed at overcoming resistance and improving clinical outcomes in ccRCC.

A 52-year-old woman with de novo metastatic, grade 1, luminal A ILC (ER+/PR+, HER2 0; Ki-67 5%) diagnosed in 2022 achieved durable disease control with systemic therapy and maintenance ribociclib plus ovarian suppression...Despite no clear radiologic progression on CT, symptomatic gastric involvement and weight loss prompted initiation of second-line weekly paclitaxel. Signet ring morphology in gastric biopsies is not pathognomonic for primary gastric carcinoma. In patients with current or prior ILC, an IHC panel incorporating breast-lineage markers (e.g., GATA3, TRPS1) and GI markers (e.g., CDX2, CK20), alongside E-cadherin status, is pivotal to avoid misdiagnosis, inappropriate surgery, and delay of systemic therapy.

The clinical deployment of ATP-competitive inhibitors-Palbociclib, Ribociclib, and Abemaciclib-has revolutionized the standard of care for hormone receptor-positive breast cancer. By recruiting the ubiquitin-proteasome system to catalytically degrade target proteins, CDK4/6-PROTACs eliminate both enzymatic activity and non-catalytic scaffolding functions, offering a mechanistically distinct strategy to overcome the structural limitations of traditional inhibitors. This review summarizes the progression from clinical inhibitors to strategies for overcoming resistance, offering insights into the future development of CDK4/6-targeted therapies.

Treating stage II and III HR + HER2 - breast cancer patients with CDK4/6 inhibitors in Austria reduces metastatic breast cancer recurrences, resulting in considerable medical benefits and economic effects.

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.

A review of the literature reveals that studies on the efficacy and tolerability of CDK 4/6 inhibitors have primarily focused on a limited number of patients aged 70 years or older. The results of these studies, similar to our study, generally indicate that efficacy and survival are similar to those in younger patients, and that dose reductions do not significantly impact survival. Furthermore, there are no studies in the literature yet that examine the relationship between the Charlson comorbidity index and survival in elderly patients with multiple comorbidities who are receiving CDK 4/6 inhibitors.

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

Baseline vitamin D status was associated with progression-free survival outcomes in patients with HR+/HER2 - metastatic breast cancer receiving ribociclib-based therapy. Patients with sufficient vitamin D levels demonstrated longer progression-free survival compared with those with vitamin D deficiency. However, given the retrospective design, limited sample size, residual confounding, and substantial censoring, these findings should be interpreted cautiously and considered exploratory and hypothesis-generating. Larger prospective studies are required to validate these observations and to clarify the potential clinical relevance of baseline vitamin D status in patients treated with CDK4/6 inhibitors.

In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of punctate epitheliopathy and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Among respondents, symptom scores were uniformly low; however, the incomplete OSDI response rate in the CDKAI group limits definitive conclusions regarding symptom burden. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

This integrative analysis characterized the ribociclib pharmacokinetic and exposure-QTcF relationship, revealed the population effect on both pharmacokinetic and QTcF response, and justified the 400-mg dose in EBC. This work illustrates the utility and impact of quantitative pharmacology in justifying different doses across different patient populations for oncology therapies.