Ibrance (palbociclib)

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.

P1/2, N=320, Recruiting, Pikavation Therapeutics, Inc. | Phase classification: P1 --> P1/2 | N=140 --> 320 | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Apr 2027

Drug sensitivity analysis showed that the DSN1 high expression group was resistant to drugs such as Epirubicin, Cyclophosphamide, Ribociclib, and Palbociclib, but relatively sensitive to tamoxifen and lapatinib. DSN1 contributes to breast cancer progression by modulating cell cycle pathways, making it a potential diagnostic and therapeutic target with clinical applicability.

Validating the genome-wide analyses, we found that resistance of breast cancer cells to the CDK4/6 inhibitor palbociclib conferred by TGFβ stimulation was functionally dependent on SOX4. Collectively, our findings reveal an apparent oncogenic function of TGFβ in promoting cell cycle progression and drug resistance through SOX4, highlighting the pro-tumorigenic role of TGFβ signaling in breast cancer progression.

P=N/A, N=6097, Active, not recruiting, Brigham and Women's Hospital | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026

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.

SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity.

Data were leveraged from preclinical and phase I/II studies in metastatic and early breast cancer, as a single agent and with palbociclib, to inform giredestrant dose selection. Our learnings challenge the MTD paradigm in drug development, particularly in targeted therapies, and demonstrate the importance of basing dose selection on the totality of evidence, including preclinical data, and may help inform the clinical development of future targeted therapies.

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

The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).

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.