Erlotinib in lung cancer - molecular and clinical predictors of outcome

Ming-Sound Tsao, Akira Sakurada, Jean-Claude Cutz, Chang-Qi Zhu, Suzanne Kamel-Reid, Jeremy Squire, Ian Lorimer, Tong Zhang, Ni Liu, Manijeh Daneshmand, Paula Marrano, Gilda da Cunha Santos, Alain Lagarde, Frank Richardson, Lesley Seymour, Marlo Whitehead, Keyue Ding, Joseph Pater, Frances A Shepherd, Ming-Sound Tsao, Akira Sakurada, Jean-Claude Cutz, Chang-Qi Zhu, Suzanne Kamel-Reid, Jeremy Squire, Ian Lorimer, Tong Zhang, Ni Liu, Manijeh Daneshmand, Paula Marrano, Gilda da Cunha Santos, Alain Lagarde, Frank Richardson, Lesley Seymour, Marlo Whitehead, Keyue Ding, Joseph Pater, Frances A Shepherd

Abstract

Background: A clinical trial that compared erlotinib with a placebo for non-small-cell lung cancer demonstrated a survival benefit for erlotinib. We used tumor-biopsy samples from participants in this trial to investigate whether responsiveness to erlotinib and its impact on survival were associated with expression by the tumor of epidermal growth factor receptor (EGFR) and EGFR gene amplification and mutations.

Methods: EGFR expression was evaluated immunohistochemically in non-small-cell lung cancer specimens from 325 of 731 patients in the trial; 197 samples were analyzed for EGFR mutations; and 221 samples were analyzed for the number of EGFR genes.

Results: In univariate analyses, survival was longer in the erlotinib group than in the placebo group when EGFR was expressed (hazard ratio for death, 0.68; P=0.02) or there was a high number of copies of EGFR (hazard ratio, 0.44; P=0.008). In multivariate analyses, adenocarcinoma (P=0.01), never having smoked (P<0.001), and expression of EGFR (P=0.03) were associated with an objective response. In multivariate analysis, survival after treatment with erlotinib was not influenced by the status of EGFR expression, the number of EGFR copies, or EGFR mutation.

Conclusions: Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.

Copyright 2005 Massachusetts Medical Society.

Source: PubMed

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