In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 3585-3585
Abstract:
3585 Background: Accumulating evidence suggests that right- and left-sided CRCs have different prognoses and different sensitivities to EGFR inhibitors in several phase3 trials. These differences might be related to different embryological origins, which are reflected in different molecular profiles of tumors. LEFTY, Nodal and ACVR2B, which are TGF-betasuperfamily, are key regulators of left-right axis during embryogenesis; these expressions control sidedness. Our aim was to evaluate whether SNPs in these genes are associated with clinical outcomes in mCRC pts enrolled in the FIRE3 trial. Methods: Genomic DNA was obtained from mCRC pts receiving cetuximab plus FOLFIRI as first-line treatment and analyzed by using PCR-based direct sequencing. Four functional SNPs in 4 genes ( LEFTY1, LEFTY2, Nodal, and ACVR2B) were tested in 305 pts in FIRE3 trial cetuximab cohort (NCT00433927). Main characteristics were the following: male/female = 207/98; median age = 64; RAS-wildtype/mutant = 195/95; median PFS = 9.6 months; median OS = 26.5 months, median follow-up time = 41.8 months. Results: In patients with left sided tumor ( N= 237), LEFTY2 rs3007716 G/G variants ( N= 14) showed shorter PFS than any A variants ( N= 222) in univariate (8.0 months (M) vs. 10.3 M, HR = 2.24, 95%CI = 1.27-3.94, P 〈 0.01) and multivariate analyses (HR = 2.12, 95%CI = 1.20-3.75, P 〈 0.01). Nodal rs1904589 T/T ( N= 36) showed longer OS than any C variants ( N= 196) in univariate analysis (50.1 m vs. 29.8 M, HR = 0.61, 95% = 0.37-1.01, P = 0.048) and multivariate analyses (HR = 0.59, 95%CI = 0.35-0.99, P = 0.046). In patients with right sided tumors ( N= 58), ACVR2B rs2268753 C/C ( N= 12) showed shorter PFS than any T variants ( N= 43) in univariate analysis (3.7 m vs. 7.7 M, HR = 1.93, 95% = 0.99-3.77, P = 0.038) and multivariate analysis (HR = 2.24, 95%CI = 1.12-4.51, P = 0.023). Conclusions: Our study showed for the first time that genetic variations in sidedness related genes are associated with PFS and OS in patients receiving cetuximab based chemotherapy, which may dependent on location.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.3585
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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