IFCT0401-bio phase II trial: Gefitinib administered as 1st-line in non-resectable adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC)-Predictive biomarkers of efficacy and survival.

8071 Background: A prospective multicentric trial evaluated gefitinib as 1st-line in non-resectable ADC-BAC. Tissue samples were collected to identify biomarkers associated with disease control, PFS and OS.,Tumor samples were classified as BAC variants or ADC other types and as non-mucinous or mucinous/mixed. PAS staining and immunohistochemistry against TTF1 and EGFR were performed. Polysomy/amplification was examined for EGFR. EGFR 18-21 and KRAS 2 exons were amplified and sequenced.,Tumor samples were collected from 65/88 eligible participants. 50 (81%) were BAC (25 non- mucinous, 25 mucinous) and 15 (19%) ADC other types. EGFR high polysomy/amplification was present in 12/50 samples (24%), EGFR and KRAS mutations in 7/56 (12.5%) and 9/50 (18%) samples respectively. PFS was 3.21 mo [IC95%, 2.85-3.70] and associated with skin toxicity (p=0.01), low PAS-staining intensity (p=0.001), high TTF1 expression (p=0.01), non-mucinous BAC (p=0.0006), no KRAS mutation (p=0.003) and presence of high EGFR polysomy/amplification alone (p=0.008) or combined with mutation (p=0.002) in univariate analysis. In multivariate analysis, PFS was associated with no KRAS mutation (HR=0.46, p=0.06) and histology other than mucinous BAC (non-mucinous BAC: HR=0.31, p=0.003; ADC other types: HR= 0.19, p=0.001). OS was 14.0 mo [11.34-22.68] and associated with PS<2 (p=0.02), respiratory symptoms score (p=0.005), non-mucinous BAC (p=0.0006), low PAS-staining intensity (p=0.03), no KRAS mutation (p=0.004), high EGFR polysomy/amplification alone (p=0.008) or combined with mutation (p<0.002) in univariate analysis. In multivariate analysis, OS was associated with PS<2 (HR=0.06, p<0.0001), no KRAS mutation (HR=0.15, p<0.0002), high EGFR polysomy/amplification or mutation (HR=0.1, p=0.0006) and rash (HR=0.30, p=0.006).,Molecular and cytological factors are independently predictive of PFS or OS in ADC-BAC treated with gefitinib. No significant financial relationships to disclose.