Buparlisib-fulvestrant combination may benefit postmenopausal HR+, HER2- breast cancer patients

Roshini Claire Anthony
13 Dec 2016
Buparlisib-fulvestrant combination may benefit postmenopausal HR+, HER2- breast cancer patients

Postmenopausal women previously treated with aromatase inhibitors (AIs) for HR-positive, HER2-negative advanced breast cancer who progressed on or after mTOR inhibitor therapy may benefit from a combination of buparlisib and fulvestrant, according to findings of the BELLE-3* study.

Postmenopausal women with HR-positive, HER2-negative advanced breast cancer who were given the PI3K inhibitor buparlisib along with fulvestrant experienced improved progression-free survival (PFS) compared with women given fulvestrant alone (median PFS, 3.9 vs 1.8 months in the buparlisib vs placebo [fulvestrant only] groups, respectively; hazard ratio [HR], 0.67, 95 percent confidence interval [CI], 0.53–0.84; p<0.001). [SABCS 2016, abstract S4-07]

“For the first time, we have evidence from a phase III clinical trial that a PI3K inhibitor is a viable treatment option in combination with endocrine therapy for HR-positive advanced breast cancer patients progressing on everolimus plus exemestane,” said Dr Angelo Di Leo from the Ospedale Misericordia e Dolce, Prato, Italy, who presented the findings at the recent San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas, US.

“This new treatment could further delay the time of starting cytotoxic chemotherapy in this particular group of patients with ER-positive disease.”

The PFS improvement for buparlisib vs placebo was more evident in women with a PIK3CA mutation (median PFS, 4.2 vs 1.6 months; HR, 0.46, 95 percent CI, 0.29–0.73; p<0.001) compared with women with PIK3CA wildtype status (median PFS, 3.9 vs 2.7 months; HR, 0.73, 95 percent CI, 0.53–1.00; p=0.026) based on circulating tumour DNA (ctDNA) analysis, as was the case in primary tumour tissue analysis (median PFS, 4.7 vs 1.4 months; HR, 0.39; p<0.001 for PIK3CA mutation and median PFS, 2.8 vs 2.7 months; HR, 0.83; p=0.117 for PIK3CA wildtype).

The objective response rate was 7.6 percent vs 2.1 percent for the buparlisib vs placebo groups, respectively, while the clinical benefit rate at 24 weeks was 24.6 percent vs 15.4 percent.

The most common grade 3/4 adverse events experienced by buparlisib vs placebo recipients were elevated alanine aminotransferase (22 percent vs 3 percent) and aspartate aminotransferase levels (18 percent vs 3 percent), and hyperglycaemia (12 percent vs 0 percent).

The 432 trial participants (median age 61 years) had been previously treated with AIs and progressed during or within 30 days of completion of mTOR inhibitor and endocrine therapy. They were randomized to buparlisib (100 mg/day) and fulvestrant (500 mg per standard of care; n=289) or placebo and fulvestrant (n=143). The most commonly used mTOR inhibitor was everolimus (99 percent).

“The trial shows the promising activity of a new class of anticancer agent, but in my opinion it is still premature to consider this agent as a new standard of care in the treatment of ER-positive advanced breast cancer patients,” said Di Leo.

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