Copyright ©The Author(s) 2016.
World J Clin Oncol. Oct 10, 2016; 7(5): 340-351
Published online Oct 10, 2016. doi: 10.5306/wjco.v7.i5.340
Table 1 Clinical trials investigating the impact of epidermal growth factor receptor blockades in colorectal cancer patients
Ref.YearSample sizeMutation statusTreatment groupsSpecial considerationsSummarized findings
Saltz et al[46]2001120EGFR +Cetuximab plus Irinotecan22.5% major objective response rate 17% radiologic response rate
Saltz et al[47]200457EGFR +Cetuximab9% (CI: 3% to 19%) partial response Median survival of 6.4 mo. P value ??
Cunningham et al[48]2004329EGFR +Cetuximab plus irinotecan vs cetuximab alone22.9% partial response in combination arm, 10.8% partial response in the cetuximab monotherapy arm No difference in OS
Jonker et al[49]2007572EGFR +Cetuximab compared to best supportive care6.1 mo OS in treatment arm vs 4.6 mo with supportive care. P = 0.005 Quality of life was better preserved in the cetuximab group (P < 0.05)
Van Cutsem et al[56]2007463EGFR+Panitumumab vs best supportive careMedian PFS 8 wk in treatment arm compared to 7.3 wk in patients receiving supportive care (HR 0.54; P < 0.0001)
Amado et al[57]2008427EGFR+ Wild type KRAS vs mutant KRASPanitumumab vs best supportive careReanalysis of Van Cutsem 2007In patients with wild type KRAS median PFS was 12.3 wk for panitumumab vs 7.3 wk for supportive care Response rates to panitumumab was 17% for patients with wild type KRAS compared to 0% in patients with mutant KRAS
Van Cutsem et al[51] CRYSTAL Trial20091198EGFR +Cetuximab plus FOLFIRI vs FOLFIRI aloneHR for PFS in combination therapy 0.85 (P = 0.048) when compared to FOLFIRI alone There was no difference in OS (HR 0.93; P = 0.31) Although not significant PFS was improved with cetuximab in patients with wild-type-KRAS (HR 0.68; P = 0.07)
Folprecht et al[55] CELIM trial2010113Wild type KRAS vs mutant KRASCetuximab plus FOLFOX vs Cetuximab plus FOLFIRI vs historical controlsNeoadjuvant settingNo survival difference between the two groups Higher response rates compared to historical controls (FOLFOX and FOLFIRI) Total 36 of 116 patients were able to receive R0 resection Improved outcomes limited to patients with wild type KRAS
Van Cutsem et al[52]20111198EGFR+ Wild type KRAS vs mutant KRASCetuximab plus FOLFIRI vs FOLFIRI alone Wild type KRAS vs mutant KRASReanalysis of data from CRYSTAL trialPatients with wild type KRAS had improvements in OS from 20 to 23.5 mo PFS from 8.4 to 9.9 mo and response rates 39.7% to 57.3% with addition of Cetuximab to FOLFIRI
Bokemeyer et al[53] OPUS study2011315Wild type KRAS/BRAF vs mutant KRAS/BRAFCetuximab plus FOLFOXImproved PFS (HR 0.567) and response (OR 2.55) in patients with KRAS wild-type tumors
Alberts et al[54] N0137 trial20122686Wild type KRAS vs mutant KRASCetuximab plus FOLFOX vs FOLFOX aloneLocally advanced diseaseNo additional benefit of Cetuximab when added to FOLFOX-6 regimen in the setting of locally advance disease