From Stanford U and CHU Nancy-France: A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer

http://www.ncbi.nlm.nih.gov/pubmed/22809813

Lung Cancer. 2012 Jul 16. [Epub ahead of print]

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

Clément-Duchêne C, Natale RB, Jahan T, Krupitskaya Y, Osarogiagbon R, Sanborn RE, Bernstein ED, Dudek AZ, Latz JE, Shi P, Wakelee HA.

Source

Stanford University, Stanford Cancer Institute, Stanford, CA, USA; Chest Department, CHU Nancy, France.

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 EGFRresistance 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 150mg/day and enzastaurin 500mg/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 1.7months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3months (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.