In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 7653-7653
Abstract:
7653 Background: A French prospective multicentric phase II trial (IFCT0401) evaluated gefitinib as first-line treatment in non- resectable ADC-BAC. Tissue samples were collected for central pathological review and molecular analysis in attempt to identify biological markers associated with DC by gefitinib. Methods: Tumor samples were classified as BAC variants or ADC-other types according to the 2004 WHO histological classification and as non-mucinous or mucinous/mixed according to cytology. Immunohistochemistry was performed using antibodies against TTF1, Ki67, phosphorylated AKT, erbB2, and EGFR. Polysomy/amplification was examined for EGFR and erbB2. EGFR 18–21 and K-ras 2 exons were amplified and sequenced. Results: Tissue specimen were collected from 65 of the 88 eligible participants. This subgroup did not differ from the overall trial population in terms of sex ratio, proportion of non-smokers and DC rate. DC was achieved in 22/64 patients (DCR=34.4%, CI=[22–41]). 81% were BAC variants (n=50) and 19% ADC other types. Of the 50 BAC variants, half were non-mucinous and half mucinous. EGFR high polysomy/amplification was present in 6/40 samples (15%). EGFR exon 19, 20 and 21 mutations were detected in 6/57 (10.5%), 1/49 (2%) and 0/58 samples, respectively and K- ras mutation in 11/53 (20.7%). Expression of TTF1 (p 〈 0.0001) and EGFR (p=0.04) as well as polysomy/amplification of EGFR (p=0.04) were significantly higher in the non-mucinous than in the mucinous type. There was also a trend for more frequent detection of EGFR mutations among non-mucinous than mucinous type (p=0.08). DC with gefitinib was significantly associated with female gender (p=0.02), non- smoker status (p=0.03), non-mucinous subtype (p=0.006), high TTF1 expression (p=0.02) and EGFR mutation (p=0.0003). K-ras mutation was associated with progression (p=0.04). Conclusions: Among patients with histologically proven ADC-BAC who received gefitinib, female gender, non-smoker status, non-mucinous subtype, high TTF1 expression, and EGFR mutation are associated with DC, while K-ras mutation is associated with disease progression. Multivariate analysis will be released at ASCO meeting. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.7653
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
Permalink
