EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study - 04/01/12
, Jose R Pereira, MD b, Joachim von Pawel, MD c, Maciej Krzakowski, ProfMD d, Rodryg Ramlau, MD e, Keunchil Park, ProfMD f, Filippo de Marinis, MD g, Wilfried EE Eberhardt, MD h, Luis Paz-Ares, MD i, Stephan Störkel, ProfMD j, Karl-Maria Schumacher, MD k, Anja von Heydebreck, PhD k, Ilhan Celik, ProfMD k, Kenneth J O’Byrne, ProfMD lSummary |
Background |
Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762–0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients.
Methods |
We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0–300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.
Findings |
Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2–15·2] vs 9·6 months [7·6–10·6]; HR 0·73, 0·58–0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9–12·2] vs 10·3 months [9·2–11·5]; HR 0·99, 0·84–1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044).
Interpretation |
High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting.
Funding |
Merck KGaA.
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Vol 13 - N° 1
P. 33-42 - janvier 2012 Retour au numéro
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