Smoking history and epidermal growth factor receptor expression as predictors of survival benefit from erlotinib for patients with non-small-cell lung cancer in the National Cancer Institute of Canada Clinical Trials Group study BR.21.

Full Abstract

BACKGROUND:
Erlotinib is an oral, reversible inhibitor of the HER1/epidermal growth factor receptor (EGFR) tyrosine kinase. A survival advantage for erlotinib compared with placebo was demonstrated in the National Cancer Institute of Canada Clinical Trials Group study BR.21, a randomized double-blind study of 731 patients with advanced-stage non-small-cell lung cancer.

PATIENTS AND METHODS:
In this retrospective, exploratory investigation, univariate and multivariate analyses of survival of the 311 patients with available EGFR status by immunohistochemistry and known smoking history were performed to determine which factor might be more important for predicting clinical outcome.

RESULTS:
A marginally significant interaction was observed between smoking history and treatment (P = 0.054). The hazard ratios (HRs) were 0.42 among never-smokers and 0.87 for smokers, indicating that erlotinib was beneficial in both subsets but more effective in patients who had never smoked. The HRs for patients with EGFR-positive and EGFR-negative tumors were 0.65 and 0.83, respectively; however, the interaction between EGFR status and treatment was not significant in univariate or multivariate analyses. Patients with EGFR-positive tumors who never smoked had the greatest survival benefit from erlotinib relative to placebo (HR, 0.28; P = 0.0007).

CONCLUSION:
These data suggest that never-smokers and patients with EGFR-positive tumors might experience an enhanced benefit from erlotinib compared with placebo but that smoking history might be more predictive of survival benefit than EGFR expression. Subset analyses of ever-smokers revealed significant survival advantages for men and patients with squamous cell histology. Male ever-smokers with squamous cell non-small-cell lung cancer derived a significant survival benefit from erlotinib (HR, 0.66; P = 0.015) despite a very low tumor response rate.

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Author information

Author/s: Clark, Gary M (GM); Zborowski, Denni M (DM); Santabarbara, Pedro (P); Ding, Keyue (K); Whitehead, Marlo (M); Seymour, Lesley (L); Shepherd, Frances A (FA); National Cancer Institute of Canada Clinical Trials Group;

Affiliation: OSI Pharmaceuticals, Inc, Boulder, CO 80301, USA. gclark(-atsign-)osip.com

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial

Journal: Clinical lung cancer (Clin Lung Cancer), published in United States. (Language: eng)

Reference: 2006-May; vol 7 (issue 6) : pp 389-94

Dates: Created 2006/06/27; Completed 2007/02/05; Revised 2007/03/08;

PMID: 16800964, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Clin Lung Cancer. 2006 May;7(6):369-70. (PMID: 16800960)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aged
Canada - epidemiology
Carcinoma, Non-Small-Cell Lung - drug therapy; etiology; metabolism; mortality; pathology
Female
Humans
Lung Neoplasms - drug therapy; etiology; metabolism; mortality; pathology
Male
Proportional Hazards Models

Proportional Hazards Models
Protein Kinase Inhibitors - therapeutic use
Quinazolines - therapeutic use
Receptor, Epidermal Growth Factor - antagonists & inhibitors; metabolism
Retrospective Studies
Risk Factors
Smoking - adverse effects
Survival Analysis

Associated Chemicals: Protein Kinase Inhibitors (0) ; Quinazolines (0) ; erlotinib (0) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112)

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