A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer.
BACKGROUND
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.
Stanford University, Stanford Cancer Institute, Stanford, CA, USA.
Christelle
C
Clément-Duchêne
Ronald B
RB
Natale
Thierry
T
Jahan
Yelena
Y
Krupitskaya
Raymond
R
Osarogiagbon
Rachel E
RE
Sanborn
Eric D
ED
Bernstein
Arkadiusz Z
AZ
Dudek
Jane E
JE
Latz
Peipei
P
Shi
Heather A
HA
Wakelee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
D007211:Indoles; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C504878:enzastaurin