Kisqali (ribociclib)

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

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.

P4, N=148, Not yet recruiting, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Mifepristone provided marked palliative benefit in this patient with nPR-negative, metastatic breast cancer, suggesting potential therapeutic value in similar cases. Confirmation of efficacy will require larger studies focused on tumors with absent or minimal nuclear progesterone receptor expression.

P1, N=396, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Jun 2027

We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

The patient began systemic therapy with ribociclib plus letrozole, achieving radiologic improvement of the cervical lesion and abdominal disease. This case highlights the ability of ILC to recur after long latency and to metastasize to unusual gynecologic sites such as the cervix. We also review the literature on cervical recurrence from lobular carcinoma to emphasize the importance of gynecologic surveillance in breast cancer survivors and to identify areas that require further investigation.

One of the most prominent milestones in the approach to targeting the cancer cell cycle was the development and approval of CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib. In this article, we focus on heterogeneous vulnerabilities of cancers as consequences of various genetic and epigenetic alterations in the cell cycle-regulatory network, and we discuss how next-generation cell-cycle-targeting drugs currently in the developmental pipeline could exploit these heterogeneous vulnerabilities in the cancer cell cycle. We hope to provide a forward-looking perspective on directions for therapeutic cell-cycle targeting in the advent of personalized precision medicine.

The results in terms of PFS and AEs are consistent with those of pivotal studies and real clinical practice data, but a direct comparison is not possible due to differences in patient populations. Ribociclib once again demonstrated efficacy in all patient subgroups and remains the gold standard, alongside ET, for first-line HR+/HER2-negative mBC.

Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole. Early ctDNA dynamic appeared a promising surrogate biomarker for treatment. Further studies are warranted to validate their clinical utility.

Drug sensitivity screening identified six small molecules (PD0325901, ERK-6604, paclitaxel, ribociclib, TAF1, and lapatinib) that targeted SLC12A5-related pathways. Crucially, multivariate Cox regression analysis confirmed that SLC12A5 was an independent prognostic factor (HR p = 0.04). This study established SLC12A5 as a novel biomarker for GBM, uniquely bridging molecular dysregulation, edema pathogenesis, and radiomics with implications for prognosis and targeted therapy.

P=N/A, N=335, Completed, Novartis Pharmaceuticals