Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer
Introduction
Cetuximab, a recombinant human/mouse chimeric monoclonal IgG1 antibody that specifically targets the epidermal growth factor receptor (EGFR), significantly improves the prognosis for metastatic colorectal cancer (MCRC) compared to best supportive care alone as a third-line treatment.1 Furthermore, the BOND-1 study, which examined over 300 patients with irinotecan-pretreated MCRC, demonstrated that combining cetuximab with irinotecan results in higher response rates and longer progression-free survival (PFS) than cetuximab alone (22.9% vs. 10.8%, respectively).2 Based on these results, cetuximab plus irinotecan has become one of the standard chemotherapies in MCRC patients after failure with 5-fluorouracil (5-FU), oxaliplatin, and irinotecan.3 Although the BOND-1 study also suggested that cetuximab may restore chemosensitivity to irinotecan in MCRC patients with irinotecan-refractory disease,2 to our knowledge, only one study has reported the relationship between the efficacies of previous irinotecan-based chemotherapy and cetuximab plus irinotecan for MCRC.4 Notably, neither this study4 nor the BOND-1 study2 evaluated KRAS status, which may have affected treatment response, on the basis of several retrospective findings that the indications for cetuximab are limited to MCRC patients with wild-type KRAS.5, 6, 7, 8, 9
Here, we examined the association of sensitivity to previous irinotecan-based chemotherapy with outcomes after cetuximab plus irinotecan treatment in MCRC patients with wild-type KRAS using a pooled data set consisting of data from two phase II studies10, 11 and a group of other eligible patients who had received off-protocol treatment.
Section snippets
Patients
We previously conducted two phase II studies to prospectively evaluate the effectiveness and safety of combination chemotherapy with weekly cetuximab plus irinotecan10 or biweekly cetuximab11 in the treatment of MCRC patients with wild-type KRAS who had experienced progression after irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. The primary end-point was response rate, and the tumour response was assessed objectively every 8 weeks according to the Response Evaluation
Patient characteristics
The present analysis was conducted between September 2008 and August 2010 in 87 patients, consisting of 60 patients in phase II clinical trials and 27 patients administered an off-protocol treatment (Table 1). Forty-nine patients (56%) received a weekly regimen of cetuximab, while the other 38 patients (44%) received a biweekly regimen, with all patients receiving biweekly irinotecan. All patients had received two or more prior chemotherapy regimens, with a median interval from initiation of
Discussion
In this study, we evaluated the relationship between sensitivity to previous irinotecan-based chemotherapy and efficacy of cetuximab plus irinotecan in MCRC patients with wild-type KRAS in whom prior chemotherapy consisting of irinotecan, oxaliplatin, or fluoropyrimidine had failed. Our results indicate that sensitivity to previous irinotecan-based chemotherapy has no association with clinical outcomes of subsequent irinotecan plus cetuximab treatment. Therefore, irinotecan plus cetuximab
Funding
None declared.
Conflict of interest statement
None declared.
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Cited by (1)
Cetuximab/irinotecan-chemotherapy in KRAS wild-type pretreated metastatic colorectal cancer: A pooled Analysis and review of literature
2013, Reviews on Recent Clinical Trials