A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer.

Abstract

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.

• Authors: Christelle Clément-Duchêne, Ronald B Natale, Thierry Jahan, Yelena Krupitskaya, Raymond Osarogiagbon, Rachel E Sanborn, Eric D Bernstein, Arkadiusz Z Dudek, Jane E Latz, Peipei Shi, Heather A Wakelee
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 78 Issue 1 Pg. 57-62 (Oct 2012) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 22809813 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Indoles
• Quinazolines
• Erlotinib Hydrochloride
• enzastaurin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Erlotinib Hydrochloride
• Female
• Humans
• Indoles (administration & dosage)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Quinazolines (administration & dosage)
• Risk Factors
• Treatment Outcome