HR positive + HER-2 negative

P3, N=331, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

This consensus uniquely contextualizes global evidence for GCC-specific healthcare constraints, addressing gaps in diagnostic access, affordability, and real-world feasibility, while providing treatment recommendations that help clinicians refine therapeutic strategies and incorporate patient preferences for improved outcomes. The panel recommends early genomic testing (PIK3CA, AKT, BRCA, ESR1) to guide therapy, prioritizing targeted agents such as oral SERDs and PI3K/AKT inhibitors in second-line sequencing, cautious use of alpelisib in diabetic patients, and incorporating patient preferences through shared decision-making and multidisciplinary care.

ctDNA-based methylation and fragmentomic profiling revealed exploratory, treatment specific molecular dynamics, highlighting biological differences between CDK4/6 inhibitors. These findings support the feasibility of liquid biopsy-based biomarker studies in this setting, although their potential clinical relevance remains preliminary and requires validation in larger cohorts with earlier and more granular on-treatment timepoints.

Palbociclib, ribociclib, and abemaciclib are approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC), in combination with aromatase inhibitors or fulvestrant...Subsequent therapies, including chemotherapy (CT), endocrine therapy (ET) with or without everolimus, and CDK4/6i-based regimens, were evaluated...These findings emphasize the variability in treatment efficacy following CDK4/6i therapy and underscore the importance of personalized treatment strategies. Further research is needed to optimize therapeutic sequences and improve patient outcomes in this setting.

The study highlights SG's clinical relevance and the challenge of translating trial efficacy into real-world outcomes, reinforcing the need for further investigation of tolerability in broader populations.

P=N/A, N=240, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Jul 2029 --> Dec 2029 | Initiation date: Jul 2025 --> Jan 2026 | Trial primary completion date: Jul 2029 --> Dec 2029

Notably, the P subtype was linked to poor prognosis, even in patients treated with endocrine therapy alone, while the NSE subtype was associated with favorable outcomes. Our findings uncover spatial and cellular heterogeneity in ILC that is not captured by existing classification approaches, offering a refined framework for risk stratification and therapeutic targeting based on tumor microenvironment architecture.

P1, N=90, Not yet recruiting, Cogent Biosciences, Inc.

Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences.

P1, N=32, Completed, Adrienne G. Waks | Active, not recruiting --> Completed

We review emerging dynamic biomarkers to guide therapeutic decision-making, spanning tissue and liquid biopsies, metabolic imaging, and microbiome profiling, that capture tumor or host-related changes over time. By contrasting Academic and Industry approaches, we advocate for a cultural shift in clinical trial design and implementation, aiming to move from reactive to proactive Oncology.

P1, N=27, Recruiting, SAPU NANO (US) LLC