Jian Chen1, Yun Ye, Haozhen Sun, Genming Shi. 1. Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. cj21_0503@163.com
Abstract
PURPOSE: To comparatively evaluate whether metastatic colorectal cancer (mCRC) patients with KRAS codon 13 mutations (codon 13 muts) can benefit from anti-EGFR treatment. METHODS: We performed a meta-analysis of relevant studies. Systematic searches of the PubMed, Embase, and Cochrane databases, as well as ASCO conference papers up to July 30, 2012, were retrieved, and the authors of included studies were contacted to obtain more individual data. Fixed effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end points were the overall response rate (ORR). Secondary end points were progress-free survival (PFS) and overall survival (OS). RESULTS: A total of 7 studies were included in the final meta-analysis, consisting of 2,802 mCRC patients, 1,679 of whom were treated with anti-EGFR monoclonal antibodies. The ORR of mCRC patients with codon 13 mutation was 25.2 % (29/115), compared to 17.6% (98/558) for other KRAS mutations (other mut) and 42.6% (429/1,006) for KRAS WT patients. The overall pooled RR for ORRs of codon 13 mut versus other mut was 1.52 (95% CI 1.10-2.09, P = 0.003), whereas the pooled RR for codon 13 mut versus WT was 0.61 (95% CI 0.45-0.83, P = 0.002). The pooled progression-free survival (PFS) times were 6.4 months for codon 13 mut, 4.1 months for other mut, and 6.6 months for WT, whereas the pooled OS durations were 14.6, 11.8, and 17.3 months, respectively. Subgroup analysis was conducted on the basis of the line of treatment, anti-EGFR drug, study design, and detection method, respectively. The results implicated that KRAS codon 13 mut patients gain more benefit from Cetuximab in further line treatment. CONCLUSIONS: Metastatic colorectal cancer patients with KRAS codon 13 mutations demonstrate a greater clinical response to anti-EGFR treatment than patients with other KRAS mutations.
PURPOSE: To comparatively evaluate whether metastatic colorectal cancer (mCRC) patients with KRAS codon 13 mutations (codon 13 muts) can benefit from anti-EGFR treatment. METHODS: We performed a meta-analysis of relevant studies. Systematic searches of the PubMed, Embase, and Cochrane databases, as well as ASCO conference papers up to July 30, 2012, were retrieved, and the authors of included studies were contacted to obtain more individual data. Fixed effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end points were the overall response rate (ORR). Secondary end points were progress-free survival (PFS) and overall survival (OS). RESULTS: A total of 7 studies were included in the final meta-analysis, consisting of 2,802 mCRC patients, 1,679 of whom were treated with anti-EGFR monoclonal antibodies. The ORR of mCRC patients with codon 13 mutation was 25.2 % (29/115), compared to 17.6% (98/558) for other KRAS mutations (other mut) and 42.6% (429/1,006) for KRAS WT patients. The overall pooled RR for ORRs of codon 13 mut versus other mut was 1.52 (95% CI 1.10-2.09, P = 0.003), whereas the pooled RR for codon 13 mut versus WT was 0.61 (95% CI 0.45-0.83, P = 0.002). The pooled progression-free survival (PFS) times were 6.4 months for codon 13 mut, 4.1 months for other mut, and 6.6 months for WT, whereas the pooled OS durations were 14.6, 11.8, and 17.3 months, respectively. Subgroup analysis was conducted on the basis of the line of treatment, anti-EGFR drug, study design, and detection method, respectively. The results implicated that KRAS codon 13 mut patients gain more benefit from Cetuximab in further line treatment. CONCLUSIONS: Metastatic colorectal cancerpatients with KRAS codon 13 mutations demonstrate a greater clinical response to anti-EGFR treatment than patients with other KRAS mutations.
Authors: Harry H Yoon; David Tougeron; Qian Shi; Steven R Alberts; Michelle R Mahoney; Garth D Nelson; Suresh G Nair; Stephen N Thibodeau; Richard M Goldberg; Daniel J Sargent; Frank A Sinicrope Journal: Clin Cancer Res Date: 2014-03-31 Impact factor: 12.531
Authors: Antonia R Sepulveda; Stanley R Hamilton; Carmen J Allegra; Wayne Grody; Allison M Cushman-Vokoun; William K Funkhouser; Scott E Kopetz; Christopher Lieu; Noralane M Lindor; Bruce D Minsky; Federico A Monzon; Daniel J Sargent; Veena M Singh; Joseph Willis; Jennifer Clark; Carol Colasacco; R Bryan Rumble; Robyn Temple-Smolkin; Christina B Ventura; Jan A Nowak Journal: J Mol Diagn Date: 2017-02-06 Impact factor: 5.568
Authors: Christin E Burd; Wenjin Liu; Minh V Huynh; Meriam A Waqas; James E Gillahan; Kelly S Clark; Kailing Fu; Brit L Martin; William R Jeck; George P Souroullas; David B Darr; Daniel C Zedek; Michael J Miley; Bruce C Baguley; Sharon L Campbell; Norman E Sharpless Journal: Cancer Discov Date: 2014-09-24 Impact factor: 39.397
Authors: Zhenhao Fang; Christopher B Marshall; Jiani C Yin; Mohammad T Mazhab-Jafari; Geneviève M C Gasmi-Seabrook; Matthew J Smith; Tadateru Nishikawa; Yang Xu; Benjamin G Neel; Mitsuhiko Ikura Journal: J Biol Chem Date: 2016-05-18 Impact factor: 5.157
Authors: Christof Fellmann; Benjamin G Gowen; Pei-Chun Lin; Jennifer A Doudna; Jacob E Corn Journal: Nat Rev Drug Discov Date: 2016-12-23 Impact factor: 84.694
Authors: Bert Vogelstein; Nickolas Papadopoulos; Victor E Velculescu; Shibin Zhou; Luis A Diaz; Kenneth W Kinzler Journal: Science Date: 2013-03-29 Impact factor: 47.728