Background and importance Treatment goals for advanced or metastatic breast cancer include not only delaying progression of the disease and extending survival, but also maintaining or improving the quality of the patient’s life. New targeted therapies, such as cyclin dependent kinase (CDK) 4/6 inhibitors, have improved patient outcomes with hormonal receptor positive, HER negative, metastatic breast cancer compared with conventional single agent endocrine therapy. They contribute to clinical benefit but at the same time they are the cause of complex and potentially severe adverse events that require good clinical management of toxicities.

Aim and objectives To assess the safety of CDK4/6 inhibitors, analysing the relevant adverse drug reactions (ADRs) and reviewing the clinical management of toxicities.

Material and methods A retrospective observational study was conducted in a second level hospital. We assessed the safety of three CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib), reviewing the medical and pharmaceutical records of all patients that attended the pharmacy department from January to March 2020. Collected data were: age, ECOG, cancer stage, metastatic location, type of CDK4/6 inhibitor in combination with endocrine therapy, ADRs, grade and clinical management (dose reductions, temporary interruptions and permanent discontinuations).

Results 58 patients were included, median age 55 years (75–39), and 67% (39) received ribociclib, 29% (17) received palbociclib and 4% (2) received abemaciclib. ECOG at the beginning was 0 in 55% (32) of patients, 1 in 28% (16) and 2 in 10% (6). 100% of patients had disease stage IV and the main metastatic location was bone (87%). Average number of cycles received was 15 (1–36). 38 (66%) patients had severe ADRs (grades 3–4), approximately 3 severe ADRs per patient. Neutropenia was the most common ADR grade 3/4 (85%) related to CDK4/6 inhibitors, and was highest with ribociclib compared with the other CDK4/6 inhibitors, followed by gastrointestinal disorders (5%). These severe ADRs required dose reductions in 15% (31), temporary interruptions in 37% (79) and permanent discontinuation of treatment in 4% (7). 19 patients also needed supportive treatments.

Conclusion and relevance In spite of the manageable safety profile of CDK4/6 inhibitors in clinical practice, the frequency of severe ADRs associated with these treatments makes consistent close monitoring of side effects and toxicity necessary due to inter-patient variability, along with practical management strategies to find the optimal therapy for each patient.

Conflict of interest No conflict of interest