Adding the PI3K inhibitor buparlisib to fulvestrant endocrine therapy improves progression-free survival (PFS) among women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer refractory to everolimus plus exemestane, according to findings from the BELLE-3 ( Identifier: NCT01633060) study presented at the 2016 San Antonio Breast Cancer Symposium.1

“This new treatment could further delay the time of starting cytotoxic chemotherapy in this particular group of patients with HR-positive disease,” said lead study author Angelo Di Leo, MD, Ospedale Misericordia e Dolce, Prato, Italy.

The PI3K/mTOR pathway and PIK3CA driver mutations have been implicated in endocrine therapy resistance, Dr Di Leo noted.

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The study authors evaluated whether adding buparlisib to fulvestrant is safe and effective for patients whose cancer had progressed during or after mTOR inhibitor therapy with everolimus.

A total of 432 patients with previous aromatase inhibitor therapy and recent disease progression on everolimus documented were enrolled and randomly assigned to receive fulvestrant plus either placebo or buparlisib.

Median PFS was 3.9 months among patients receiving buparlisib and 1.8 months for those receiving placebo; 6-month PFS was 30.6% and 20.1%, respectively, Dr Di Leo said. Overall response rates (ORR) were 7.6% vs 2.1%, respectively.

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The researchers were able to test for PIK3CA mutations using tumor or blood samples, and there was good concordance in mutation detection between these 2 tumor DNA sources.

“Testing for PIK3CA mutations seems to be relevant because buparlisib does not seem to have relevant activity in the absence of the mutation,” Dr Di Leo said.


  1. BELLE-3: A phase III study of buparlisib + fulvestrant in postmenopausal women with HR+, HER2–, aromatase inhibitor-treated, locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor-based treatment. Paper presented at: 39th San Antonio Breast Cancer Symposium; Dec 2016; San Antonio, TX.