The combination of endocrine therapy (ET) with a cyclin-dependant kinase 4/6 inhibitor (cdk4/6i) has recently become the standard-of-care first-line therapy for advanced estrogen-receptor positive, human epidermal growth factor 2 negative (ER+/HER2-) breast cancer.
Safety data in clinical trials indicate that ribociclib is well tolerated in the trial population. This study aimed to examine the safety and toxicity of ribociclib in the real-world, non-trial population.
This retrospective study collected data from 68 patients across two tertiary hospitals. All patients had commenced on ribociclib and ET between 01/06/2017 and 30/06/2019. Adverse events (AEs) were graded by CTCAE v5.0. QTcF was recorded at baseline, 2 weeks, and 4 weeks. Dose interruptions (DIs), dose reductions (DRs) and drug cessations (DCs) were recorded.
Neutropenia occurred in 85.9% of patients - accounting for 59 DIs, 14 DRs, but no DCs. Febrile neutropenia occurred in 2 patients. AST and ALT derangement occurred in 32.8% and 37.5% of patients. Grade 3-4 events were uncommon (3.1% and 7.7%) and accounted for 3 DIs, 3 DRs and 1 DC. Grade 1 and 2 creatinine rise was common (40.6% and 7.8%) leading to 3 DIs and 2 DRs. Grade 1, 2, and 3 QTcF prolongation occurred in 24.6% and 4.9%, and 4.9% of patients, and led to 11 DIs, 3 DRs and 1 DC. Other significant reasons for DIs were surgery (17), infection (6), and for radiation (4). Gastrointestinal AEs led to 6 DRs. 22 patients ceased ribociclib--11 due to progressive disease. ILD/pneumonitis occurred in 1 patient, necessitating a DC. There was 1 death on ribociclib.
Ribociclib in combination with ET is well-tolerated. AEs are manageable with DIs and DRs and rarely necessitate DC. Data collected in our cohort of patients indicate that ribociclib is a safe and tolerable first-line treatment in advanced breast cancer in clinical practice.