Elsevier

Clinical Therapeutics

Volume 27, Issue 10, October 2005, Pages 1513-1534
Clinical Therapeutics

New drug review
Erlotinib: Small-molecule targeted therapy in the treatmentof non-small-cell lung cancer

https://doi.org/10.1016/j.clinthera.2005.10.014Get rights and content

Abstract

Background:

Erlotinib is an oral tyrosine kinase inhibitor, 1026 targeting the human epidermal receptor type 1/ epidermal growth factor receptor, recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after the failure of more than 1 or 2 previous chemotherapeutic regimens.

Objective:

The purpose of this article is to summarize1026 the development, pharmacology, pharmacokinetics, efficacy, and adverse effects of erlotinib.

Methods:

A literature search was conducted with 1026 the MEDLINE and EMBASE (1999–2005) databases using the search terms non-small-cell lung cancer, erlotinib, and epidermal growth factor receptor inhibitor. Abstracts from the American Society of Clinical Oncology and documents submitted to the FDA also were reviewed.

Results:

BR.21, a randomized, placebo-controlled, 1026 multinational Phase III trial demonstrated clinically and statistically improved overall survival in patients with advanced or metastatic NSCLC treated with erlotinib versus placebo as second-line therapy. The erlotinib group had a median survival of 6.7 months versus a median survival of 4.7 months in the placebo group (P < 0.001). The toxicity profile of erlotinib was moderately benign, with the most commonly documented adverse events requiring dose reductions including skin rash (12%) and diarrhea (5%). Interstitial lung disease and relative fatalities were reported infrequently (0.8%) in patients receiving erlotinib. Two randomized, placebo-controlled, multicenter Phase III trials conducted in patients with locally advanced and metastatic NSCLC showed no clinical benefit with first-line administration of erlotinib plus concurrent platinum-based chemotherapy.

Conclusions:

For patients with NSCLC in whom1026 more than 1 or 2 previous chemotherapeutic regimens have failed, erlotinib is an effective therapy with significant overall survival benefits. The use of erlotinib as first-line therapy in combination with platinum-based chemotherapeutic regimens, however, has failed to demonstrate efficacy in the treatment of NSCLC.

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