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 TTP 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 TTP of BMs, ORR, OS, PFS, or HRQoL after WBRT in LC patients with BMs.