RT Journal Article
T1 A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).
A1 Martín, M
A1 Chan, A
A1 Dirix, L
A1 O'Shaughnessy, J
A1 Hegg, R
A1 Manikhas, A
A1 Shtivelband, M
A1 Krivorotko, P
A1 Batista López, N
A1 Campone, M
A1 Ruiz Borrego, M
A1 Khan, Q J
A1 Beck, J T
A1 Ramos Vázquez, M
A1 Urban, P
A1 Goteti, S
A1 Di Tomaso, E
A1 Massacesi, C
A1 Delaloge, S
K1 HER2−
K1 PI3K pathway
K1 advanced breast cancer
K1 breast cancer
K1 buparlisib (BKM120)
K1 paclitaxel
AB Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II.
YR 2017
FD 2017
LK http://hdl.handle.net/10668/10569
UL http://hdl.handle.net/10668/10569
LA en
DS RISalud
RD Apr 13, 2025