The efficacy of alpelisib in luminal HER2-negative breast cancer with brain metastases: clinical cases.

Abstract

Introduction. Hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (BC) with the PIK3CA gene mutations is associated with high incidence of brain metastases. Data on the efficacy of target therapy in metastatic brain lesions, especially in symptomatic metastases, are limited because the brain metastases are usually the exclusion criteria in clinical trials and only patients with previously treated and radiologically stable brain metastases may be eligible for the study.

Materials and methods. The article presents two clinical cases of patients with HR+/HER2- advanced breast cancer with mutations in the PIK3CA gene and brain metastases treated with alpelisib combined with fulvestrant. The first patient with multiple brain, lung, liver and bone metastases received alpelisib combined with fulvestrant in fifth-line treatment that lasted for nine months. Target lesion in front lobe disappeared, other intra- and extracranial metastases stabilized without radiotherapy. The second patient with multiple brain, lung and bone metastases received alpelisib combined with fulvestrant in ninth-line treatment that lasted for 18+ months. As a result, brain metastases stabilized, and extracranial symptoms partially regressed. Prior to drug therapy, the patient had received whole brain radiotherapy. However, the prolonged, 10-month reduction in brain metastases after remote radiotherapy may indicate the anti-tumor effect of alpelisib combined with fulvestrant. Both cases had manageable toxicity. In one patient, the dose of alpelisib was reduced by one dose level due to grade 2 nausea; in the second patient, no dose adjustment was required.

Conclusion. These clinical cases demonstrate the efficacy of alpelisib combined with fulvestrant for brain metastases.