PI3K inhibitor provides durable response in metastatic metaplastic carcinoma of the breast: A hidden gem in the BELLE-4 study

J Formos Med Assoc. 2019 Sep;118(9):1333-1338. doi: 10.1016/j.jfma.2018.12.004. Epub 2018 Dec 18.

Abstract

Purpose: Metaplastic carcinoma of the breast (MCB) is a rare cancer characterized by the histologic presence of two or more histological cell types originating from epithelial and mesenchymal stem cells. Patients with metastatic MCB have a low response rate to conventional chemotherapy and poor survival. Optimal treatment strategies for metastatic MCB are urgently needed.

Methods: We retrospectively reviewed a patient who had enrolled in the phase II/III seamless study, BELLE-4 (NCT01572727). The patient's response to the study drug assessed by an investigator per protocol and clinical course were examined and compared with those of the main cohorts in the BELLE-4 study.

Results: Our patient exhibited metastatic MCB and received systemic chemotherapy, paclitaxel (70 mg/m2/week) and buparlisib (80 mg/day), a pan-class I phosphatidylinositol-3 kinase (PI3K) inhibitor. The optimal response was a confirmed partial response for 17 months in total. During the compassionated use program period, the tumor regrew when buparlisib was stop because of toxicity, and responded to the treatment again after resumed the buparlisib treatment. The overall survival of the patient after the development of metastatic MCB was 42 months. She experienced grade 3 hyperglycemia similar to that observed in the main cohort.

Conclusion: Buparlisib plus weekly paclitaxel might be a new treatment option for patients with metastatic MCB harboring a PIK3CA mutation. Additional prospective studies for investigating the efficacy of the proposed combination are warranted.

Keywords: BELLE-4; Buparlisib; Metaplastic breast cancer; Phosphatidylinositol 3-kinases inhibitor; Triple-negative breast cancer.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Aminopyridines / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Carcinoma / drug therapy*
  • Female
  • Humans
  • Metaplasia / pathology
  • Morpholines / administration & dosage*
  • Paclitaxel / administration & dosage*
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Aminopyridines
  • Morpholines
  • NVP-BKM120
  • Phosphoinositide-3 Kinase Inhibitors
  • Paclitaxel