Introduction: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.
Methods: We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.
Results: The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.
Conclusion: This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512091 | PMC |
| http://dx.doi.org/10.1016/j.breast.2023.05.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cellular senescence offers distinct immunological vulnerabilities in cancer.
Trends Cancer
December 2024
Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA; Immunology and Microbiology Program, University of Massachusetts Chan Medical School, Worcester, MA, USA; Cancer Center, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address:
Chronic damage following oncogene induction or cancer therapy can produce cellular senescence. Senescent cells not only exit the cell cycle but communicate damage signals to their environment that can trigger immune responses. Recent work has revealed that senescent tumor cells are highly immunogenic, leading to new ways to activate antitumor immunosurveillance and potentiate T cell-directed immunotherapies.
View Article and Find Full Text PDFTargeting CDK2 to circumvent treatment resistance in HR breast cancer.
Trends Mol Med
December 2024
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:
Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.
View Article and Find Full Text PDFSelf-assembled natural triterpenoids for the delivery of cyclin-dependent kinase 4/6 inhibitors to enhance cancer chemoimmunotherapy.
J Control Release
December 2024
Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475000, PR China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475000, PR China; Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China. Electronic address:
Immunogenic cell death (ICD) has recently emerged as a promising strategy in reinforcing anti-PD-L1 blockade immunotherapy of triple-negative breast cancer (TNBC). The CDK4/6 inhibitor palbociclib (PAL), as a clinical star medicine targeting the cell cycle machinery, is an ideal candidate for fabricating a highly efficient ICD inducer for TNBC chemoimmunotherapy. However, the frequently observed chemoresistance and clinical adverse effects, as well as significant antagonistic effects when co-administered with certain chemotherapeutics, have seriously restricted the efficiency of PAL and the feasibility of combination strategies.
View Article and Find Full Text PDFDiscovery of a novel CDK4/6 and HDAC dual-targeting agent for the treatment of hepatocellular carcinoma.
Bioorg Chem
December 2024
The State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
The down-regulation of p21 after long-term CDK4/6 inhibition represents a key mechanism causing resistance to CDK4/6 inhibitors in some tumor cells, while the HDAC inhibitor could upregulate the level of p21. Herein, a series of novel CDK4/6 and HDAC dual-targeting inhibitors based on the moiety of palbociclib were designed and synthesized. Among them, compound N14 potently inhibited CDK4/6 and HDAC1/6 at nanomolar levels and induced cell apoptosis and G/G phase arrest through HDAC-p21-CDK signaling pathway in HuH-7 cell line.
View Article and Find Full Text PDFCDK4/6 inhibitors in HR-positive breast cancer immunotherapy.
Bioorg Chem
December 2024
Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China. Electronic address:
Breast cancer is the most prevalent malignant tumour among women. Approximately 70 % of patients are hormone receptor (HR)-positive and undergo endocrine therapy as the main form of treatment; however, the efficacy of this type of therapy is limited by some factors, such as drug resistance and complex tumour microenvironments. Using network pharmacology and molecular docking, this study examined how CDK4/6 inhibitors enhance the effects of immunotherapy for HR-positive breast cancer, focusing on their effects on the tumour microenvironment (TME) and immune cell activity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!