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KRAS status and resistance to epidermal growth factor receptor tyrosine‐kinase inhibitor treatment in patients with metastatic colorectal cancer: a meta‐analysis
Author(s) -
Li W.,
Shi Q.,
Wang W.,
Liu J.,
Ren J.,
Li Q.,
Hou F.
Publication year - 2014
Publication title -
colorectal disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.029
H-Index - 89
eISSN - 1463-1318
pISSN - 1462-8910
DOI - 10.1111/codi.12749
Subject(s) - medicine , cetuximab , kras , hazard ratio , colorectal cancer , oncology , meta analysis , subgroup analysis , panitumumab , gastroenterology , cancer , confidence interval
Aim This study reviewed the association between KRAS mutation and resistance to treatment with epidermal growth factor receptor ( EGFR ) tyrosine‐kinase inhibitors ( TKI s) in patients with metastatic colorectal cancer (m CRC ). Method A search was carried out of P ub M ed, MEDLINE , EMBASE and the C ochrane L ibrary databases (to November 2013) without language restrictions. Results Ten studies were included in the final meta‐analysis, consisting of 1339 patients with m CRC , of whom 427 (32%) had a KRAS mutation. The objective response rate ( ORR ) of m CRC patients with KRAS mutation was 8% (33/427), whereas the ORR of m CRC patients with wild‐type KRAS was 34% (306/912). The overall pooled response rate ( RR ) for the ORR was 1.297 (95% CI 1.244–1.353, P < 0.01). Subgroup analysis comparing cetuximab monotherapy treatment with cetuximab plus chemotherapy, showed a pooled RR of 1.26 (95% CI 1.12–0.63, P < 0.01) and 1.30 (95% CI 1.25–1.36, P < 0.01), respectively. For patients receiving anti‐ EGFR with monoclonal antibodies (m A b) given as first‐line treatment or not, the pooled RR s were 1.34 (95% CI 1.23–1.46, P < 0.01) and 1.29 (95% CI 1.23–1.35, P < 0.01). The data on progression‐free survival from five studies in the meta‐analysis gave a hazard ratio ( HR ) of 1.99 with a 95% CI of 1.69–2.29. Finally, the data for overall survival in mCRC patients were pooled from the only three studies reporting the HR (1.80; 95% CI 1.50–2.10). None of the results had any evidence of heterogeneity. Conclusion All the results favoured a stronger link between mutant KRAS and anti‐ EGFR m A b, but due to a mutually exclusive relationship between KRAS and other gene mutations the clinical usefulness of KRAS mutation as a selection marker for sensitivity to EGFR TKI s in m CRC is limited.