A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fulvestrant; BKM120; BKM120 matching placebo
Intervention description: Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter); BKM120 100 mg once daily; BKM120 matching placebo, once daily
Intervention MeSH terms: Fulvestrant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 432.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BKM120; fulvestrant; breast cancer; metastatic; locally advanced; AI treated; mTOR inhibitor; PI3K; PIK3CA; PTEN; HER2-; HR+

Summary:

      This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to
      determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo
      plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human
      epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor
      (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or
      after mammalian target of rapamycin inhibitor (mTORi)-based treatment.

      Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in
      combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg.
      Randomization was stratified according to visceral disease status (present or absent).
    

Eligibility criteria:

        Key inclusion criteria

          -  Female patients age 18 years or older

          -  Histologically and/or cytologically confirmed diagnosis of breast cancer

          -  Radiologic evidence of inoperable locally advanced or metastatic breast cancer

          -  Adequate tumor tissue for the analysis of PI3K-related biomarkers

          -  Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive
             hormone receptor status

          -  Postmenopausal women

          -  Prior treatment with aromatase inhibitors

          -  Evidence of progression to the combination of mTORi and endocrine therapy given as the
             last therapy prior to study entry

          -  Adequate bone marrow and organ function

          -  ECOG performance status ≤ 2

        Key exclusion criteria

          -  Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant

          -  More than one chemotherapy line for metastatic disease

          -  Hypersensitivity to any of the excipients of buparlisib or fulvestrant

          -  Symptomatic central nervous system metastases

          -  Concurrent malignancy or malignancy within 3 years of study enrollment

          -  Certain drugs or radiation within 2-4 weeks of enrollment

          -  Increasing or chronic treatment (>5 days) with corticosteroids or another
             immunosuppressive agent

          -  Certain scores on an anxiety and depression mood questionnaire given at screening

          -  Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis
             C virus

          -  Active cardiac disease or a history of cardiac dysfunction