W Li1, Q Shi, W Wang, J Liu, J Ren, Q Li, F Hou. 1. Oncology Department, Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, China.
Abstract
AIM: This study reviewed the association between KRAS mutation and resistance to treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with metastatic colorectal cancer (mCRC). METHOD: A search was carried out of PubMed, MEDLINE, EMBASE and the Cochrane Library databases (to November 2013) without language restrictions. RESULTS: Ten studies were included in the final meta-analysis, consisting of 1339 patients with mCRC, of whom 427 (32%) had a KRAS mutation. The objective response rate (ORR) of mCRC patients with KRAS mutation was 8% (33/427), whereas the ORR of mCRC 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 (mAb) given as first-line treatment or not, the pooled RRs 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 mAb, 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 TKIs in mCRC is limited. Colorectal Disease
AIM: This study reviewed the association between KRAS mutation and resistance to treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with metastatic colorectal cancer (mCRC). METHOD: A search was carried out of PubMed, MEDLINE, EMBASE and the Cochrane Library databases (to November 2013) without language restrictions. RESULTS: Ten studies were included in the final meta-analysis, consisting of 1339 patients with mCRC, of whom 427 (32%) had a KRAS mutation. The objective response rate (ORR) of mCRC patients with KRAS mutation was 8% (33/427), whereas the ORR of mCRC 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 (mAb) given as first-line treatment or not, the pooled RRs 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 mAb, 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 TKIs in mCRC is limited. Colorectal Disease
Authors: Jonathan P Evans; Boleslaw K Winiarski; Paul A Sutton; Robert P Jones; Lorenzo Ressel; Carrie A Duckworth; D Mark Pritchard; Zhi-Xiu Lin; Vicky L Fretwell; Elizabeth M Tweedle; Eithne Costello; Christopher E Goldring; Ian M Copple; B Kevin Park; Daniel H Palmer; Neil R Kitteringham Journal: Oncotarget Date: 2018-06-05