Kisqali (ribociclib)

P3, N=5101, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2026 --> May 2030 | Trial primary completion date: May 2026 --> May 2030

This single-centre retrospective observational cohort study included patients with HR+/HER2- metastatic breast cancer treated with endocrine therapy and a CDK4/6 inhibitor (palbociclib or ribociclib) in the metastatic setting between January 2018 and May 2025. However, modelling BMI as a continuous variable revealed a non-linear (U-shaped) relationship, with increased risk at both the low and high ends of the BMI distribution. These findings suggest that the prognostic impact of BMI is non-linear and may be obscured by simple dichotomous categorisation.

We retrospectively analyzed 156 women with HR+/HER2- MBC (hormone-receptor-positive, Her2-negative metastatic breast cancer) who initiated ribociclib or palbociclib plus endocrine therapy between May 2020 and January 2024. Routine body composition assessment may refine risk stratification and identify candidates for supportive interventions. Prospective studies are needed to validate these findings.

A total of 100 patients were evaluable 53 treated with palbociclib, 44 with ribociclib and 3 with abemaciclib. Pretreatment sTILs levels were associated with outcome in patients treated with palbociclib. Given the lack of interaction between treatment and sTILs our findings warrant validation in larger, independent cohorts and if confirmed propose sTILs as a simple and reproducible biomarker to aid patient selection for palbociclib.

P2/3, N=172, Active, not recruiting, Novartis Pharma AG | Recruiting --> Active, not recruiting

P1/2, N=564, Recruiting, AstraZeneca | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027

We ran a BIA to evaluate two scenarios: (1) Increasing abemaciclib's market share from 20% to 60%, replacing both palbociclib and ribociclib. In addition, ribociclib and abemaciclib are affordable treatment options if they equally contributes to up to 80% of the market share for the eligible advanced breast cancer patients. The results supported the concept of allocating CDK4/6 inhibitors as they were found to be affordable to the Qatari healthcare system.

P2/3, N=312, Not yet recruiting, Olema Pharmaceuticals Inc.

P=N/A, N=329, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=388, Not yet recruiting, Fudan University

Eligibility criteria for adjuvant abemaciclib (monarchE) and ribociclib (NATALEE) trials were applied. Conclusion A substantial proportion of Colombian patients with HR+/HER2- early breast cancer qualify for adjuvant CDK4/6i, particularly those with nodal involvement. These findings highlight both the clinical opportunity and economic challenges of implementing these therapies in resource-limited settings while underscoring the need for improved early detection to reduce advanced presentations. Eligibility based on clinical-pathological criteria identifies a high-risk group, though optimal selection may require biomarker refinement where available.

Using HR+/HER2- BC models with acquired resistance to the CDK4/6 inhibitors Palbociclib or Ribociclib, we uncovered a metabolic vulnerability in highly resistant clones, mediated by mTORC1 hyperactivation and autophagy suppression. Gene expression profiling revealed enrichment of glycolysis and mTORC1 pathways in CDK4/6i-resistant cells, which manifested as heightened sensitivity to the metabolic inhibitors Metformin and Dichloroacetate (DCA)...Clinically, immunohistochemical analysis of a BC cohort revealed a significant correlation between mTORC1 activity (p4E-BP1T37/46) and autophagy suppression (p62 accumulation), supporting the translational relevance of this axis. Our findings propose mTORC1-mediated autophagy defects as a biomarker for metabolic vulnerability in CDK4/6i-resistant BC, offering a rationale for targeting these tumors with metabolic therapies to overcome resistance.