Novartis' (VTX:NOVN) buparlisib faces an uphill battle in improving overall survival (OS) in the BELLE-2 Phase III breast cancer trial to an extent that it would justify its side-effect profile, said experts.
Targeting the PI3K pathway as buparlisib does would cause significant side effects, since it is involved in a number of cellular functions, experts said. The number of patients that discontinued treatment due to side effects adversely affected the drug's risk-benefit profile, they added.
Due to the large number of treatments patients receive, especially those that are still hormone-receptor (HR) positive, it has become challenging to associate an OS improvement with a particular drug, experts said. The Phase III is being conducted in HR+, HER2-negative postmenopausal women with locally advanced or metastatic disease.
BELLE-2 (NCT01610284) data, released at the San Antonio Breast Cancer Symposium (SABCS) in December 2015, showed that buparlisib met the trial's primary endpoint of progression-free survival (PFS). But the magnitude of benefit in light of the observed side-effect profile prompted expert caution.