The data presented were gathered from a multicenter Phase II study of enzastaurin as a second- or third-line treatment of NSCLC (ASCO Abstract #7543 ). The rationale for the study was based on en-zastaurins unique mechanism of action as a serine/threonine kinase inhibitor, which is believed to suppress signaling through the PKC- and PI3K/AKT pathways. Historically, over-expression and ac-tivity of PKC- and PI3K/AKT have been associated with poor prognosis and treatment resistance in NSCLC. The primary objective of the study was progression-free survival at six months. Secondary endpoints were safety and overall survival at 12 months.
These data in NSCLC shed new light on the potential versatility of this agent, said Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader for Lilly. Our objective with enzastaurin is to continue investigating the efficacy and safety of this unique molecule in order to determine the diseases where enzastaurin could have the most positive impact on patients.
In the study, patients received 500 mg of oral enzastaurin, once daily, until disease progression or un-acceptable toxicity occurred. In the 54 patients enrolled, the median progression-free survival was 1.9 months (95% Confidence Interval: 1.7-1.9) and the progression-free survival rate at six months was 14% (95% CI: 4.4%-23.6%). The median overall survival was 9.9 months (95% CI: 6.5-14.6). The overall survival rate at 12 months was 46.3% (95% CI: 32.1%-60.5%). The most common toxicity was fatigue. Additional toxicities observed included ataxia (n=1), thromboembolism (n=1), anemia (n=1) and dizziness.
Based on the encouraging survival and tolerability data gathered thus far, further evaluation of en-zastaurin in NSCLC, as a single agent or in combination, is warranted, said chief investigator for the study, Gerold Bepler, M.D., Ph.D., chief of thoracic oncology at the H. Lee Moffitt Cancer Center and Research In
Contact: Neil Hochman