Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor

Abstract

Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptorpositive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on efficacy and tolerability, abemaciclib is a potentially convenient, safe, and effective agent for the treatment of patients with advanced hormone receptor-positive patients. Orally administered abemaciclib in combination with aromatase inhibitors or fulvestrant has the potential to allow significant improvement in survival outcomes, quality of life, response rate, and duration of response even in poor prognosis subgroups. Adequate patients' information, clinical selection, and prompt, proactive management of side effects are mandatory.

Cyclin-dependent kinase 4/6 inhibitors and interstitial lung disease in the FDA adverse event reporting system: a pharmacovigilance assessment

“…Because of inherent limitations [ 10 – 12 , 28 ], including no certainty on causation, incomplete/missing information, and potential codification errors, these findings raise the hypothesis that a drug-specific susceptibility exists for ILD, and ask per se for additional analytical studies, such as population-based investigation, to confirm the signal before any regulatory action other than information or harmonization of SPCs can be envisioned [ 30 ]. In particular, this study cannot be used to quantify ILD risk and provide risk ranking mainly because: (a) under-reporting and the lack of data on population exposure do not actually allow calculation of incidence rate; (b) the diagnosis depends on a number of criteria, including radiological assessment and the exclusion of other causes such as prior radiotherapy, which cannot be obtained with absolute certainty.…”

Prediction of severe neutropenia and diarrhoea in breast cancer patients treated with abemaciclib

“…Supplementary 12 [8][9][10][11][12][13][14][15][16] 21 [9-32] 14 [9][10][11][12][13][14][15][16][17][18][19] 21 [9-32] 16 [11][12][13][14][15][16][17][18][19][20][21][22] 37 J o u r n a l P r e -p r o o f Supplementary…”

“…The regulatory approval [ 11 ] and existing literature [ 12 ] present limited information about risk factors associated with developing diarrhoea and neutropenia in patients initiating abemaciclib. Development of clinical prediction models of diarrhoea and neutropenia using routinely collected clinicopathological data following abemaciclib therapy may assist clinicians in providing personalized toxicity risks.…”

Abemaciclib in Patients with End-Stage Renal Disease and Advanced Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Report of 2 Cases

“…Such combination therapy achieves a considerable advantage in median disease-free and overall survival with good toxicity profile in ER+, her-2− breast cancer patients [6, 7]. Among the three clinically available CDKIs, abemaciclib is the most potent agent in preclinical studies, determines a survival advantage in metastatic disease, and has also recently shown a progression-free survival advantage in the adjuvant setting [8, 9]. After oral administration, abemaciclib is mainly excreted via the feces after hepatic metabolism, primarily involving the CYP3A4 cytochrome, while renal excretion is responsible only for 3% of its clearance [10].…”