Objectives: We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database.
Methods: The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs.
Results: 16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3-4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33-41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1-4: RR: 2.23, 95% CI: 1.25 - 3.96; grade 3-4: RR: 3.52, 95% CI: 1.59 - 8.11) and palbociclib (grade 1-4: RR: 1.65, 95%CI: 1.03 - 2.59), but a lower risk of grade 3-4 of both leukopenia (RR: 0.12, 95%CI: 0.02 - 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 - 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors.
Conclusion: Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks.
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http://dx.doi.org/10.1080/14740338.2024.2348566 | DOI Listing |
Int J Oncol
February 2025
Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229HX Maastricht, The Netherlands.
Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in , loss of or activation of receptor tyrosine kinases. In HPV‑negative tumors, (encoding p16 protein) inactivation or (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines.
View Article and Find Full Text PDFESMO Open
January 2025
UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, USA.
Background: 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, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.
View Article and Find Full Text PDFFront Oncol
December 2024
Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
The most frequently used standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer patients consists of a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) combined with endocrine therapy. Despite CDK4/6 inhibitors being part of routine care in the last few years, new adverse events continue to be reported. Here, we report two cases of palinopsia, a rare neurological visual disturbance that refers to the persistence or recurrence of a visual image after the removal of visual stimuli in patients treated with ribociclib and letrozole.
View Article and Find Full Text PDFBMC Cancer
December 2024
Ankara Bilkent City Hospital, Department Of Medical Oncology, Ankara Yildirim Beyazit University, Ankara, 06800, Turkey.
Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials.
View Article and Find Full Text PDFCurr Oncol
November 2024
Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, Turkey.
Background/objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort.
Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey.
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