Enzastaurin shows promise as second- or third-line therapy in NSCLC

March 27, 2008

NEW YORK (Reuters Health) - Enzastaurin, an oral serine/threonine kinase inhibitor, halted disease progression in some patients with metastatic non-small-cell lung cancer (NSCLC) in a single-arm, phase II study published in the March 1 issue of the Journal of Clinical Oncology.

The results of therapy with enzastaurin fell somewhat short of the study's planned primary end point of a 6-month progression-free survival (PFS) rate of 20%, a threshold based on published results for gefitinib. Nonetheless, the researchers concluded that, based in part on enzastaurin's low toxicity, the drug does have potential in patients with advanced NSCLC, likely in combination with a cytotoxic agent.

Dr. Gerold Bepler of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, enrolled 55 patients aged 44 to 82 years (median 63 years) in a phase II study of the agent. Most had an ECOG performance status of 1 and stage IV disease. Study participants had to have experienced relapse or disease progression on previous platinum-based therapy. The most common diagnosis was adenocarcinoma (65%).

Enzastaurin (500 mg/day in cycles of 28 days) was given as second-line therapy in 32 patients, as third-line therapy in 21 and as fourth-line therapy in 2.

The PFS rate at 6 months was 13%, and the median PFS was 1.8 months. Nineteen patients were progression-free for at least 2 months, and 3 were progression-free for more than 10 months. The median overall survival time was 8.4 months, and the overall survival rate at 12 months was 44%.

Fatigue was the most common adverse effect (n = 17), and ataxia, pulmonary embolism and anemia were the only grade 3 toxicities related to the enzastaurin treatment. Two patients discontinued enzastaurin therapy because of adverse effects related to it, but there were no drug-related deaths.

There are two possible approaches to using enzastaurin, Dr. Bepler told Reuters Health. "One possibility is to find patients whose tumors have specific molecular features that would make enzastaurin highly effective as a single-agent therapy, and the other possibility is to combine enzastaurin with another 'targeted' agent."

Dr. Bepler added that several trials of enzastaurin in combination with chemotherapy are under way, such as one trial using enzastaruin plus pemetrexed for second-line therapy in patients with NSCLC. A study is also under way to see whether enzastaurin might be effective for lung cancer prevention.