Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study
A partir de données issues de l'essai de phase III FLEX évaluant l'ajout du cetuximab à une combinaison cisplatine-vinorelbine dans le cancer du poumon non à petites cellules, cette étude rétrospective évalue divers biomarqueurs susceptibles de prédire la réponse thérapeutique
Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened forKRAScodon 12 and 13 andEGFRkinase domain mutations with PCR-based assays. In FFPE tissue sections,EGFRcopy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered withClinicalTrials.gov, numberNCT00148798. KRASmutations were detected in 75 of 395 (19%) tumours and activatingEGFRmutations in 64 of 436 (15%).EGFRcopy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. ActivatingEGFRmutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7?23·4] vs 8·5 months [7·1?10·8], hazard ratio [HR] 0·52 [0·32?0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2?not reached] vs 10·0 months [8·7?11·0], HR 0·35 [0·21?0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6?13·6] vs 6·8 months [5·9?12·7], HR 0·80 [0·55?1·16], p=0·24; chemotherapy alone: 11·0 months [9·2?12·6] vs 9·3 months [7·6?11·9], HR 0·77 [0·54?1·10], p=0·16). The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Merck KGaA.
The Lancet Oncology , résumé, 2010