Phase I Study of the Pan-PI3K Inhibitor Buparlisib in Adult Chinese Patients with Advanced Solid Tumors.

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Phase I Study of the Pan-PI3K Inhibitor Buparlisib in Adult Chinese Patients with Advanced Solid Tumors.

Anticancer Res. 2016 Nov;36(11):6185-6194

Authors: Wu YL, Zhang LI, Trandafir L, Dong T, Duval V, Hazell K, Xu B

Abstract
BACKGROUND/AIM: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in cancer. Buparlisib (BKM120), an oral pan-PI3K inhibitor, inhibits proliferation of human cancer in preclinical models. Studies of buparlisib in Western and Japanese adults with advanced solid tumors established a recommended dose of 100 mg/day and showed an acceptable safety profile and evidence of efficacy. This phase I dose-escalation/expansion study aimed to establish the maximum tolerated dose (MTD) of single-agent, once daily oral buparlisib in Chinese patients with advanced solid tumors.
MATERIALS AND METHODS: Patients (n=32; primary tumor site: lung (n=15), breast (n=10) or head and neck (n=7); ≥2 prior lines of antineoplastic therapy (n=26)) received 80 mg (n=15) or 100 mg (n=17) daily buparlisib.
RESULTS: Five patients experienced dose-limiting toxicities: grade (G)3 depression (n=1), G2 hyperglycemia (n=3) and G3 hyperglycemia (n=1). Most frequent buparlisib-related adverse events were hyperglycemia (n=18; 56%), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase (n=9; 28%), as well as anxiety (n=6; 19%); most common buparlisib-related G3/4 adverse events: hyperglycemia (n=3; 9%), ALT and AST increase (n=2; 6%), as well as gamma-glutamyltransferase increase (n=2; 6%). Best response was stable disease (SD) in 10 patients (31%).
CONCLUSION: The MTD of buparlisib was declared as 100 mg/day. Safety, efficacy and pharmacokinetic data from this study were similar to those previously reported in Western and Japanese populations.

PMID: 27793950 [PubMed - in process]

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