Abstract

Background Next to KRAS mutation status, additional predictive markers are needed for the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Previous studies indicated that germline polymorphisms in specific genes may predict efficacy and toxicity of cetuximab in mCRC patients. Methods Germline DNA was isolated from 246 KRAS wild-type mCRC patients who were treated in the phase III CAIRO2 study with chemotherapy and bevacizumab alone or with the addition of cetuximab. Associations of epidermal growth factor ( EGF) 61A > G, EGF receptor ( EGFR) CA 14–22, cyclin D1 ( CCND1) 932G > A, fragment-C gamma receptor ( FCGR) 2A 535A > G and FCGR3A 818A > C polymorphisms with progression-free survival (PFS) and cetuximab-related skin toxicity were studied. Results In cetuximab-treated patients, the FCGR3A 818C-allele was associated with decreased PFS compared with the FCGR3A 818AA genotype (median PFS, 8.2 [95%CI, 6.7–10.3] versus 12.8 [95%CI, 10.3–14.7] months, respectively; HR, 1.57 [95%CI, 1.06–2.34]; P = .025). The EGFR ⩾ 20 genotype was associated with decreased PFS compared with the EGFR < 20 genotype (median PFS, 7.6 [95%CI, 6.7–10.0] versus 12.4 [95%CI, 10.3–13.4] months, respectively; HR, 1.58 [95%CI, 1.06–2.35]; P = .024). The FCGR3A and EGFR polymorphisms were not associated with PFS in patients treated without cetuximab. None of the polymorphisms were associated with the incidence of grades 2–3 skin toxicity. Conclusion EGFR and FCGR3A germline polymorphisms are associated with PFS in KRAS wild-type mCRC patients treated with cetuximab, bevacizumab and chemotherapy.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call