BACKGROUND: Randomised controlled trials (RCTs) of anti-EGFR monoclonal antibodies (MAb) in patients with advanced colorectal cancer (aCRC) have reported conflicting results. METHODS: A systematic review of RCTs comparing standard treatments±anti-EGFR MAbs was conducted. Hazard ratios (HR) for progression-free (PFS) and overall survival (OS) were derived for patients with wild-type (WT) and mutant KRAS. Prespecified analyses were conducted for line of treatment, MAb used, chemotherapy regimen, and choice of fluouropyrimidine. Trials using bevacizumab on both arms were included in a sensitivity analysis. RESULTS: Fourteen eligible RCTs were identified, with results by KRAS status available for ten RCTs. For third line treatment, the effect of anti-EGFR MAbs depended on KRAS status (interaction p<0.00001), with a PFS benefit for patients with WT KRAS only (HR=0.43, 95% CI 0.35-0.52, p<0.00001). For first and second line treatment, the effect also appeared to depend on KRAS status (interaction p=0.0003), again with the PFS benefit only for patients with WT KRAS (HR=0.83, 95% CI 0.76-0.90, p<0.0001). Differences between trial results (heterogeneity p=0.02, I(2)=62%) were best explained by the fluouropyrimidine used, with PFS benefits confined to trials combining MAbs alongside 5FU-based chemotherapy (HR=0.77, 95% CI 0.70-0.85, p<0.00001). There was no evidence of a PFS benefit when MAbs were given with bevacizumab. CONCLUSIONS: For aCRC patients with WT KRAS, there are clear benefits of anti-EGFR MAbs in the third line and in the first and second line, when used alongside infusional 5FU-based regimens. However, there is no benefit for patients with KRAS mutations.
BACKGROUND: Randomised controlled trials (RCTs) of anti-EGFR monoclonal antibodies (MAb) in patients with advanced colorectal cancer (aCRC) have reported conflicting results. METHODS: A systematic review of RCTs comparing standard treatments±anti-EGFR MAbs was conducted. Hazard ratios (HR) for progression-free (PFS) and overall survival (OS) were derived for patients with wild-type (WT) and mutant KRAS. Prespecified analyses were conducted for line of treatment, MAb used, chemotherapy regimen, and choice of fluouropyrimidine. Trials using bevacizumab on both arms were included in a sensitivity analysis. RESULTS: Fourteen eligible RCTs were identified, with results by KRAS status available for ten RCTs. For third line treatment, the effect of anti-EGFR MAbs depended on KRAS status (interaction p<0.00001), with a PFS benefit for patients with WT KRAS only (HR=0.43, 95% CI 0.35-0.52, p<0.00001). For first and second line treatment, the effect also appeared to depend on KRAS status (interaction p=0.0003), again with the PFS benefit only for patients with WT KRAS (HR=0.83, 95% CI 0.76-0.90, p<0.0001). Differences between trial results (heterogeneity p=0.02, I(2)=62%) were best explained by the fluouropyrimidine used, with PFS benefits confined to trials combining MAbs alongside 5FU-based chemotherapy (HR=0.77, 95% CI 0.70-0.85, p<0.00001). There was no evidence of a PFS benefit when MAbs were given with bevacizumab. CONCLUSIONS: For aCRC patients with WT KRAS, there are clear benefits of anti-EGFR MAbs in the third line and in the first and second line, when used alongside infusional 5FU-based regimens. However, there is no benefit for patients with KRAS mutations.
Authors: Mei-Yin C Polley; Boris Freidlin; Edward L Korn; Barbara A Conley; Jeffrey S Abrams; Lisa M McShane Journal: J Natl Cancer Inst Date: 2013-10-17 Impact factor: 13.506
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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
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Authors: Mary E Charlton; Amanda R Kahl; Alissa A Greenbaum; Jordan J Karlitz; Chi Lin; Charles F Lynch; Vivien W Chen Journal: J Natl Compr Canc Netw Date: 2017-12 Impact factor: 11.908