Buparlisib Phase III Findings: Glass Half Empty or Half Full?
Results from the phase 3 BELLE-3 trial demonstrated prolonged progression-free survival for the combination of the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib plus fulvestrant vs placebo plus fulvestrant in postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer after treatment with an aromatase inhibitor and the mammalian target of rapamycin (mTOR) inhibitor everolimus. At 6 months, the rate of progression-free survival was 31% for those in the buparlisib arm vs 20% for patients in the placebo arm—representing a 33% improvement favoring buparlisib (P < .001). Moreover, the combination of buparlisib and fulvestrant appeared to have the best results in PI3K-mutated breast cancer and in patients with visceral metastases.
However, the combination of buparlisib plus fulvestrant was associated with toxicities: particularly concerning were adverse events in more than 10% of patients, which included elevated transaminase levels and psychiatric symptoms such as depression and anxiety.
Ruth O’Regan, MD, of the University of Wisconsin-Madison, a coauthor of the study, noted that patients who did not benefit from prior mTOR treatment did achieve a benefit from buparlisib. “This supports the idea that PI3K inhibitors can be used in patients whose cancers don’t respond to mTOR inhibition,” she stated. Discussion after the presentation of the trial results at the 2016 San Antonio Breast Cancer Symposium suggested that newer PI3K-targeted therapies selective for the PI3K-alpha isoenzyme may be as effective yet less toxic.