Prognostic Parameters of Palbociclib in HR+/HER2- Advanced Breast Cancer: A Narrative Review

Wang, Wenxian; Wu, Jiayi; Chen, Keyu; Wang, Xiaojia; Shao, Xiying

doi:10.1177/15330338231173504

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…Finally, we examined the combined effect of reparixin with tamoxifen, fulvestrant, and two CDK4/6 inhibitors such as palbociclib and ribociclib which are currently being used in treatment of endocrine resistant breast cancer therapy [ 23 ]. Palbociclib and ribociclib have shown the overall survival (OS) clinical benefits with AIs and fulvestrant in HR+/HER2− advanced breast cancer (ABC) patients in the studies of MONALESSA-2, MONARCH-3, PALOMA-2 [ 24 , 25 ]. We treated ERBC cells with reparixin, tamoxifen, fulvestrant, palbociclib, and ribociclib by the single and combination treatment.…”

Section: Resultsmentioning

confidence: 99%

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast

Pandithar,

Galke,

Akume

et al. 2024

Mol Biol Rep

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Background ER positive breast cancer is currently targeted using various endocrine therapies. Despite the proven therapeutic efficacy, resistance to the drug and reoccurrence of tumor appears to be a complication that many patients deal with. Molecular pathways underlying the development of resistance are being widely studied. Methods and results In this study, using four established endocrine resistant breast cancer (ERBC) cell lines, we characterized CXCL1 as a secreted factor in crosstalk between ERBC cells and fibroblasts. Protein array revealed upregulation of CXCL1 and we confirmed the CXCL1 expression by real-time qRT-PCR and U-Plex assay. Co-culturing ERBC cells with fibroblasts enhanced the cell growth and migration compared to monoculture. The crosstalk of ERBC cells with fibroblasts significantly activates ERK/MAPK signaling pathway while reparixin, CXCR1/2 receptor inhibitor, attenuates the activity. Reparixin displayed the ERBC cell growth inhibition and the combination treatment with reparixin and CDK4/6 inhibitor (palbociclib and ribociclib) increased these inhibitory effect. Conclusions Taken together, our study implicates CXCL1 as a critical role in ERBC growth and metastasis via crosstalk with fibroblast and cotargeting CXCR1/2 and CDK4/6 could potentially overcome endocrine resistant breast cancer.

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Section: Resultsmentioning

confidence: 99%

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast

Pandithar,

Galke,

Akume

et al. 2024

Mol Biol Rep

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Beyond clinical trials: CDK4/6 inhibitor efficacy predictors and nomogram model from real‐world evidence in metastatic breast cancer

Liu,

Hu,

Xie

et al. 2024

Cancer Innovation

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BackgroundCDK4/6 inhibitors (CDK4/6i) have shown promising results in the treatment of hormone receptor‐positive (HR+) metastatic breast cancer (MBC) when combined with endocrine therapy (ET). It is crucial to evaluate the actual effectiveness and safety of CDK4/6i in clinical practice, as well as to analyze the factors that can predict their outcomes.MethodsPatients with HR+ MBC who received CDK4/6i‐based therapy between May 2016 and May 2023 at Hunan Cancer Hospital were evaluated for progression‐free survival (PFS). Adverse reactions were assessed based on the National Cancer Institute Common Toxicity Criteria (version 5.0).ResultsThis study included 344 patients, with a median PFS (mPFS) of 12.8 months (range: 10.4–15.2 months). After adjustment, Cox multivariate regression analysis revealed that visceral metastasis (specifically liver and brain metastases), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 1, estrogen receptor ≤ 80%, progesterone receptor ≤ 10%, Ki‐67 > 30%, and treatment in later stages were significant factors associated with reduced PFS. Based on this, we created a prognostic nomogram and validated its performance, obtaining a C‐index of 0.714 (95% confidence interval: 0.640–0.787) as well as reliable calibration and clinical impact. The mPFS of CDK4/6i rechallenge was 7.7 months; for patients who initially discontinued CDK4/6i for reasons other than disease progression, CDK4/6i rechallenge still provided a mPFS of 11.4 months. The tolerability and safety of combining CDK4/6is with ET were manageable. Adverse events led to treatment discontinuation in 3.8% of patients. Neutropenia (29.1%), leukopenia (13.7%), and anemia (4.1%) were the primary grade 3/4 adverse reactions.ConclusionsThis real‐world study highlights the ample efficacy and reasonable safety of combined CDK4/6i and ET in patients with HR+ MBC. Individualized treatment decisions and ongoing safety monitoring are important to optimize the therapeutic benefit of CDK4/6i treatment.

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Factors Affecting the Survival of Metastatic Breast Cancer Patients Treated With Cdk 4/6 Inhibitors

Isleyen¹,

Muglu²,

Topcu³

et al. 2024

Preprint

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Objective We aim to determine the efficacy, and the factors associated with the effectiveness of first-line CDK4/6i (ribociclib or palbociclib) in HR-positive, HER2-negative MBC patients. Material and method This is a retrospective, cross-sectional, and descriptive study. Ninety patients with metastatic breast cancer receiving CDK 4/6i from three different oncology clinics were included in the study. Results Of the patients, 56 (62.2%) had received ribociclib, and 34 (37.8%) palbociclib. There was no significant difference between the groups regarding age, gender, comorbidities, ECOG performance status, and menopausal status (p>0.05). The cut-off values for ER, PR, and Ki-67 levels were determined by ROC curve analysis. It was found as 80% for ER level, 50% for PR level, and 30% for Ki-67 level. PFS was significantly longer in patients with ER-level greater than 80% and Ki-67 expression less than 30% in multivariate analysis. Among the patients included in our study, the median PFS was 22.41 months in the patients with only a Ki-67 level of 30% and above, while the median PFS was 17.24 months in the patients with only an ER level of 80% and below. In the patients with a combined ER of 80% or less, and a Ki-67 of 30% or more, the median PFS was 12.42 months (p<0.001). Conclusion This study demonstrated that CDK4/6i therapies had longer PFS in patients with ER levels greater than 80% and Ki-67 expression less than 30%. It is essential to determine which patient group benefits more from first-line CDK4/6is.

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Prognostic Parameters of Palbociclib in HR+/HER2- Advanced Breast Cancer: A Narrative Review

Cited by 3 publications

References 39 publications

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast

Beyond clinical trials: CDK4/6 inhibitor efficacy predictors and nomogram model from real‐world evidence in metastatic breast cancer

Factors Affecting the Survival of Metastatic Breast Cancer Patients Treated With Cdk 4/6 Inhibitors

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