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

Phase 3 Terminated 432 enrolled Novartis Pharmaceuticals

RandomizedParallel-groupQuadruple-blindTreatment

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).

Timeline

Start: 2012-10-03
Primary completion: 2016-05-23
Completion: 2017-09-21

Outcome

Met primary endpoint

Stopped: “Novartis decided not to pursue further development of buparlisib program (assessment of moderate PFS benefit with know, but manageable, buparlisib profile).”

registry analysis (other test); BKM120 100mg + Fulvestrant vs Placebo + Fulvestrant; p <0.001; Hazard Ratio (HR) 0.67; Log Rank NCT01633060 ↗

Publications

Di Leo A, Johnston S, Lee KS, Ciruelos E, Lonning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csoszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):87-100. doi: 10.1016/S1470-2045(17)30688-5. Epub 2017 Dec 7.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Buparlisib	Small molecule	100 mg	Oral
Background	Fulvestrant	Small molecule	500 mg	Intramuscular