Safety Profile of Buparlisib Plus Fulvestrant in Advanced Breast Cancer
In a study published in The Lancet, although buparlisib plus fulvestrant was determined to be an effective treatment of postmenopausal women with relapsed HER2-negative, locally advanced or metastatic breast cancer, the combination treatment was nonetheless deemed unsafe due to associated adverse effects. Thus, Angelo Di Leo, MD, of the Nuovo Ospedale di Prato Santo Stefano in Prato, Italy, and colleagues do not recommend further development of this combination therapy in this setting.
In the randomized, double-blind, placebo-controlled, phase III BELLE-3 trial, 432 patients took part. They had histologically or cytologically confirmed hormone receptor–positive breast cancer and were pretreated with mTOR inhibitors; 289 were randomly assigned to the phosphoinositide 3-kinase (PI3K) buparlisib plus the endocrine therapy fulvestrant group, and the remaining 143 were assigned to the placebo group.
The most frequent grade 3–4 adverse events in the buparlisib plus fulvestrant group were elevated alanine aminotransferase levels (22%), elevated aspartate aminotransferase levels (18%), hyperglycemia (12%), hypertension (6%), and fatigue (3%). Serious adverse events were reported in 64 patients (22%) in the combination therapy group versus 23 patients (16%) in the placebo group.
In terms of efficacy, the median progression-free survival in the buparlisib plus fulvestrant group was 3.9 months compared with 1.8 months for the placebo group. Thus, Dr. Di Leo and colleagues suggest continued investigation of other PI3K inhibitors plus endocrine therapy in the treatment of patients with PIK3CA mutations.