Implementing alpelisib with fulvestrant in metastatic breast cancer treatment: safety profile, findings from real-world clinical data

Breast cancer is the most common cancer diagnosed among women in 2021in Croatia, according to the last published data by the Croatian National Cancer Registry. For hormonally dependent – HER2 negative metastatic breast cancer (HR+HER2– mBC) patients with PIK3CA mutations, a PIK3CA inhibitor alpelisib,combined with fulvestrant has demonstrated efficacy following prior treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, as shown in clinical trials such as SOLAR-1 and BYLieve. In this analysis we discuss alpelisib implementation in real-world practice, emphasizing similarities with the clinical trials and available data for several real-world trials. In a cohort of 20 women with HR+/HER2– mBC, patient demographics, treatment duration, adverse events (AEs), and reasons for treatment discontinuation were analyzed. Seventy percent of patients experienced treatment-related adverse events (AEs), most frequently hyperglycemia, rash, and oral mucositis, over the median three-month course of alpelisib. In 65% of cases, adverse events (AEs) required dosage modifications or interruptions, and 40% of patients discontinued their treatment. Our real-world findings show a higher frequency of AEs and less favorable treatment tolerance, compared to clinical trial data. These findings are consistent with prior real-world studies but differ from the more rigorous compliance and monitoring in clinical trials. Our results highlight the importance of improved safety procedures and monitoring to improve treatment compliance in real-world settings. It highlights awareness of how challenging it is to manage therapy-related toxicity in standard clinical practice, which can affect treatment sustainability.