Palbociclib as an Antitumor Drug: A License to Kill DOI Creative Commons
Agnieszka Łupicka‐Słowik, Federica Cossu, Marcin Sieńczyk

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5334 - 5334

Published: Nov. 13, 2024

Neoplastic cells are characterized by uncontrolled cell divisions caused cycle dysregulation. Key regulatory proteins governing the transition from G1 to S phase CDK4 and CDK6 kinases, which controlled D-type cyclins. The CDK4/6 kinases enable use of these as targets for anticancer therapy because they prevent growth development malignant inhibiting their activity. This paper surveys clinical trial results concerning palbociclib, first in-class FDA-approved drug hormone-dependent breast cancer. It discusses therapeutic applications in cancer well solid tumors hematopoietic malignancies. Additionally, presents an analysis palbociclib resistance acquired during explores new approaches, such modifications that enhance its desired activity or open up possibilities (PROTACs).

Language: Английский

Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2− metastatic breast cancer in the US real-world setting DOI Creative Commons
Hope S. Rugo, Rachel M. Layman, Filipa Lynce

et al.

ESMO Open, Journal Year: 2025, Volume and Issue: 10(1), P. 104103 - 104103

Published: Jan. 1, 2025

Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, findings. This study HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination an aromatase inhibitor (AI), US clinical practice.

Language: Английский

Citations

3
Real-World Experience with CDK4/6 Inhibitors in the First-Line Palliative Setting for HR+/HER2− Advanced Breast Cancer DOI Creative Commons
Ram Patel, John D. Mathews, Caroline Hamm

et al.

Current Oncology, Journal Year: 2025, Volume and Issue: 32(1), P. 52 - 52

Published: Jan. 20, 2025

Introduction: CDK4/6 inhibitors in combination with aromatase (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across inhibitors, but overall (OS) outcomes varied. This study aimed to evaluate real-world PFS and OS palbociclib ribociclib when combined AIs patients HR+/HER2− advanced Materials Methods: was retrospective chart review of adult cancer treated at single academic center between 1 January 2015 December 2022. The baseline demographics, clinical characteristics, details were extracted. A Kaplan–Meier analysis used estimate OS, differences groups assessed using log-rank test. Cox proportional hazards models constructed adjust confounding factors. Results: Seventy-five included final analysis. cohort predominantly female (98.7%) postmenopausal (77.3%), 52.0% having de novo stage IV disease. Palbociclib prescribed 74.7% patients, 25.3%. receiving significantly younger (57.6 vs. 67.5 years, p = 0.013) more likely be premenopausal (42.1% 5.4%, < 0.001). median 20.3 months (95% CI: 14.8–46) 37.2 20.3–not reached [NR]), respectively. For ribociclib, not reached. adjusting age menopausal status found no significant (HR 0.92, 0.86) or 0.95, 0.92). Conclusion: In this analysis, consistent results from landmark trials, although observed shorter. ribociclib-treated had numerically longer compared those palbociclib, statistically significant. discontinuation rates similar two groups.

Language: Английский

Citations

0
Palliative Radiotherapy in Metastatic Breast Cancer Patients on CDK4/6 Inhibitors: Safety Analysis DOI Open Access
Furkan Ceylan,

Mirmehdi Mehdiyev,

Burak Bi̇lgi̇n

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 424 - 424

Published: Jan. 27, 2025

Purpose: CDK4/6 inhibitors require meticulous monitoring due to their potential cause hematological toxicities and hepatotoxicity. This study evaluates the safety of combining with palliative radiotherapy in patients metastatic hormone receptor-positive HER2-negative breast cancer. Patients Methods: included 188 treated between January 2021 June 2024. Data on patient demographics, tumor characteristics, treatment interventions were extracted from medical records. The primary focus was incidence grade ≥ 3 hematologic hepatotoxicity, assessed according CTCAE 5.0 criteria, those receiving concurrent radiotherapy. Results: With a median follow-up 18.5 months, 18-month PFS OS rates 67% 85%, respectively. age 57.5 years, 79% post-menopausal. Bone liver metastases present 66% 23% patients, Concurrent administered 25% cohort. toxicity comparable who received did not. Ribociclib use associated lower (OR: 0.37), neutropenia 0.41), dose interruptions 0.30), reductions 0.37). Pre-menopausal status linked fewer 0.17). Rates interruption, reduction, withdrawal 55%, 24%, 2%, Conclusions: does not increase adverse events

Language: Английский

Citations

0
CDK4/6 Inhibitors in Patients with Breast Cancer: A Review of Adverse Event Profiles and Recommendations for Supportive Care Interventions DOI
Kathryn Post,

Mia Holtze,

Steven J. Isakoff

et al.

Current Breast Cancer Reports, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 14, 2025

Language: Английский

Citations

0
Adjuvant CDK4/6 inhibitors in breast cancer: Interpreting trial design, evidence, and uncertainty DOI Creative Commons
Saroj Niraula

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 136, P. 102944 - 102944

Published: April 20, 2025

Language: Английский

Citations

0
Real-World Data with CDK4/6 Inhibitors—A Single Center Experience from Croatia DOI Open Access
Iva Skočilić, Marin Golčić, Ana Marija Bukovica

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(9), P. 895 - 895

Published: Aug. 23, 2024

Background: There are limited real-world data (RWD) regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in western Balkan. The aim our study was thus to analyze factors influencing progression-free survival (PFS) and overall (OS), along with differences adverse effects CDK therapy a tertiary healthcare center Croatia. Methods: We evaluated medical demographic for 163 consecutive patients metastatic breast cancer treated CDK4/6 at least one month, from October 2018, after drug became available Eligible were those who palbociclib, ribociclib, or abemaciclib. Results: median PFS treatment 2.2 years (95% CI 1.8–3.3), longest ongoing 5.4 years. Treatment first line associated longer compared second beyond (HR 0.50, 95% 0.3–0.9), without liver metastasis exhibited 0.46, 0.2–0.8) (both p < 0.05). Regarding choice inhibitors, ribociclib palbociclib 0.49, 0.29–0.82) (p = 0.0032), although effect not statistically significant when separating first-line 0.59, 0.29–1.2), second- later-line (0.49, 0.15–1.55); trend present both lines, however. presence 0.04), initial luminal A grade 0.039), time up 5 0.002) only that remained multivariate analysis. Median OS since diagnosis disease 4.5 3.9–6.3), start 3.7 3.4–4.4), while 15.8 13.8–18.3). no difference based on inhibitor 0.44) adjuvant hormonal 0.12), nonsignificant better regardless whether it first- second/later-line therapies > In analysis, 0.0003) under primary 0.03) worse OS. Conclusions: Our provides RWD HR+/HER2− cancer. To best knowledge, there Balkan; thus, valuable everyday clinical practice this region Europe, bridging gap between randomized trials reality

Language: Английский

Citations

2
Cost-effectiveness of CDK4/6 inhibitors in HR+/HER2− metastatic breast cancer: a systematic review and meta-analysis DOI
Prajakta P. Masurkar, Prachi Prajapati, Joanne Canedo

et al.

Current Medical Research and Opinion, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Sept. 21, 2024

Cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors have emerged as a significant advancement in the treatment of HR+/HER2- metastatic breast cancer (MBC). Despite clinical efficacy CDK cancer, there remains gap understanding their cost-effectiveness, particularly regarding long-term economic impact and key drivers costs, when used combination with endocrine therapy. This study aims to systematically review conduct meta-analysis cost-effectiveness studies evaluating CDK4/6 advanced identify costs

Language: Английский

Citations

2
Dose reduction and discontinuation due to the combination of CDK4/6 inhibitors and endocrine drugs: a systematic review and meta-analysis DOI
Ping Yang, Hengheng Zhang,

Meijie Wu

et al.

European Journal of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

Citations

1
MONALEESA-2 Trial—A Beacon of Hope DOI

Mayank Tripathi,

Kumar Vineet

Indian Journal of Surgery, Journal Year: 2024, Volume and Issue: 87(1), P. 221 - 222

Published: May 24, 2024

Language: Английский

Citations

0
Confirming the efficacy and safety of CDK4/6 inhibitors in the first-line treatment of HR+ advanced breast cancer: a systematic review and meta-analysis DOI Creative Commons
Xin Guan, Mengyuan Li, Xingyue Ji

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer China. Our study aims to evaluate efficacy safety CDK4/6 by processing survival data using fractional polynomial modeling methods.

Language: Английский

Citations

0