Introduction: Regardless of epidermal growth factor receptor (EGFR) mutation status, erlotinib improves survival for patients with advanced non-small cell lung cancer (NSCLC) after one or more chemotherapy regimens. Enzastaurin is an oral serine/threonine kinase inhibitor. This phase II study was designed to evaluate the efficacy and safety of erlotinib and enzastaurin in NSCLC, a combination with promise to overcome EGFR resistance based on preclinical models. Methods: Eligible patients with advanced NSCLC (IIIB or IV) who had failed one or two prior systemic treatment regimen(s) were enrolled and received erlotinib 150. mg/day and enzastaurin 500. mg/day (after a 1125-mg loading dose on day 1, cycle 1), both orally in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: From January 2008 to July 2009, 49 patients were enrolled: 29 (59%) men and 20 (41%) women; 8 (16%) were non-smokers. The median PFS was 1.7. months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3. months (95% CI: 5.3-14.3). Five patients had partial response, for an overall response rate of 10.2%; the disease control rate was 30.6% (responders. +. 10 patients with stable disease). Grade 3-4 drug-related adverse events in ≥5% of patients were diarrhea, acne, and nausea. One possibly drug-related death due to interstitial lung disease occurred during the study. Conclusions: In previously treated, unselected, advanced NSCLC patients, the addition of enzastaurin to erlotinib did not improve PFS, response, or OS compared with historical data of single-agent erlotinib, but was well tolerated.
Bibliographical noteFunding Information:
The authors acknowledge the efforts of Noelle Gasco of Eli Lilly and Company for editorial assistance and Sarita Dubey, MD, and other co-investigators for patient accrual and treatment on this trial. The study described in this publication was supported by Eli Lilly and Company and in part by the Stanford NIH/NCRR CTSA award number UL1 RR025744.
T. Jahan has received grant support from Eli Lilly and Company. C. Clément-Duchêne, Y. Krupitskaya, R.B. Natale, R. Osarogiagbon, R.E. Sanborn, and E. Bernstein declare no relevant financial conflicts of interest. A.Z. Dudek participated in advisory boards for Eli Lilly and Company 3 years ago. J.E. Latz and P. Shi are employees of Eli Lilly and Company with ownership of Lilly stock. H.A. Wakelee has received grant support from Eli Lilly and Company and Genentech for clinical trial work.