A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer

Introduction: Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs). Methods: Patients with LC (any histology) who had received WBRT for BMs were randomized to receive oral maintenance enzastaurin (1125 mg on Day 1 followed by 500 mg daily) or placebo. The primary endpoint was time to progression (TTP) of BMs. Results: Fifty-four patients received enzastaurin and 53 patients received placebo. The median UP of BMs was (months) enzastaurin: 6.9 (95% confidence interval [CI]: 3.4-11.9); placebo: 4.9 (95% CI: 3.6-not assessable); p = 0.82. Median overall survival (OS) was (months) enzastaurin: 3.8 (95% CI: 2.6-5.6); placebo: 5.1 (95% CI: 3.7-5.7); p = 0.47. Median progression-free survival (PFS) was (months) enzastaurin: 2.2 (95% CI: 1.1-2.3); placebo: 2.0 (95% CI: 1.3-2.3); p = 0.75. The overall response rate (ORR) for extracranial disease was enzastaurin: 0%; placebo: 4.5% (p = 0.49) and for intracranial disease was enzastaurin: 9.3%; placebo 6.8% (p = 0.71). Grade 4 hematologic treatment-emergent adverse events were (enzastaurin vs. placebo) thrombocytopenia (5.6% vs. 1.9%) and neutropenia (5.6% vs. 0%). There was 1 treatment-related death in each arm (enzastaurin: unknown cause; placebo: pulmonary embolism). No significant differences in health-related quality of life (HRQoL) were observed. Conclusions: Enzastaurin was well tolerated but did not improve UP of BMs, ORR, OS, PFS, or HRQoL after WBRT in LC patients with BMs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.