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

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.

• Authors: Yi-Long Wu, L I Zhang, Lucia Trandafir, Tuochuan Dong, Vincent Duval, Katharine Hazell, Binghe Xu
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 11 Pg. 6185-6194 (11 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27793950 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Aminopyridines
• Antineoplastic Agents
• Morpholines
• NVP-BKM120
• Phosphoinositide-3 Kinase Inhibitors

Topics

• Adult
• Aged
• Aminopyridines (pharmacology, therapeutic use)
• Antineoplastic Agents (therapeutic use)
• China
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Morpholines (pharmacology, therapeutic use)
• Neoplasms (drug therapy)
• Phosphoinositide-3 Kinase Inhibitors