High EGFR gene copy number and skin rash as predictive markers for EGFR tyrosine kinase inhibitors in patients with advanced squamous cell lung carcinoma
Menée sur des échantillons tumoraux prélevés sur 71 patients atteints d'un carcinome épidermoïde avancé du poumon, cettte étude suggère que le nombre de copies du gène EGFR, évalué par hybridation in situ en fluorescence, permet d'identifier, en combinaison avec l'observation d'une éruption cutanée, les patients les plus susceptibles de bénéficier d'un traitement par gefitinib ou erlotinib
Purpose: This study is aimed to search for predictors of EGFR tyrosine kinase inhibitors (TKI) efficacy in previously treated patients with advanced squamous cell lung carcinoma in which EGFR mutations are very rare. Experimental Design: EGFR gene copy numbers was assessed by fluorescence in situ hybridization (FISH) and was evaluated as predictors of EGFR-TKI efficacy in 71 patients with advanced squamous cell lung cancer who received gefitinib or erlotinib as a second-line or higher therapy. The tumors were classified into EGFR/FISH-positive (high polysomy/gene amplification) and EGFR/FISH-negative (other) groups. Results: EGFR/FISH was positive in 19 (26.7%) patients. Only EGFR/FISH positive status was correlated with the EGFR-TKIs response (EGFR/FISH+ vs EGFR/FISH-, 26.3% vs 2.0%; P = 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (hazard ratio [HR] of EGFR/FISH+ vs EGFR/FISH-, 0.57; P = 0.057] or patients experiencing grade ≥2 rash (HR for rash grade ≥2 vs <2, 0.54; P = 0.042), compared with EGFR/FISH-negative patients or those experiencing grade <2 rash, respectively. When the combined criteria of EGFR/FISH and skin rash severity were analyzed, EGFR/FISH-negative patients with grade <2 rash had poorer clinical outcomes than patients with positive EGFR/FISH or grade ≥2 rash, apparent as a lower response rate (0.0% vs 21.4%; P = 0.003) and a shorter median progression-free survival (1.13 months vs 3.90 months; P = 0.0002). Conclusions: EGFR/FISH and skin rash severity may be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population.
Clinical Cancer Research , résumé, 2012