Erlotinib in lung cancer - molecular and clinical predictors of outcome

Area of Science:

• Oncology
• Molecular Biology

Background:

• A clinical trial indicated erlotinib offers a survival advantage in non-small-cell lung cancer (NSCLC) compared to placebo.
• Investigated the association between tumor biomarkers (EGFR expression, gene amplification, and mutations) and erlotinib response and survival.

Purpose of the Study:

• To determine if epidermal growth factor receptor (EGFR) expression, amplification, or mutations in NSCLC tumors correlate with patient response to erlotinib.
• To assess the impact of these EGFR biomarkers on survival outcomes in patients treated with erlotinib.

Main Methods:

• EGFR expression was assessed using immunohistochemistry in 325 NSCLC specimens.
• EGFR mutations were analyzed in 197 samples, and EGFR gene copy number was analyzed in 221 samples from the clinical trial.
• Univariate and multivariate analyses were performed to evaluate biomarker associations with response and survival.

Main Results:

• Univariate analysis showed longer survival with erlotinib in patients with EGFR expression (HR, 0.68; P=0.02) or high EGFR gene copy number (HR, 0.44; P=0.008).
• Multivariate analysis linked adenocarcinoma, never smoking, and EGFR expression to objective response.
• However, multivariate analysis revealed that EGFR expression, gene copy number, or mutations did not significantly influence survival after erlotinib treatment.

Conclusions:

• EGFR mutations may enhance responsiveness to erlotinib in NSCLC patients.
• The presence of an EGFR mutation is not a reliable indicator of a survival benefit when treated with erlotinib.