Direct Comparison of the Efficacy and Safety of Anti-EGFR Antibodies in the Combined Therapy of Chemotherapy-Refractory Metastatic Colorectal Cancer
The combination of anti-EGFR therapy with irinotecan has brought benefits to patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) in clinical studies. Results of a study directly comparing the efficacy of two different EGFR inhibitors, panitumumab and cetuximab, in combination with irinotecan have been published in the European Journal of Cancer.
Targeted Therapy for Chemotherapy-Refractory mCRC
Cetuximab and panitumumab are monoclonal antibodies that bind to the extracellular domain of the epidermal growth factor receptor (EGFR), inhibiting the receptor's binding to its ligand and blocking the proliferative signaling cascade. Both antibodies have demonstrated benefits in overall survival compared to supportive care in clinical trials for patients with chemotherapy-refractory mCRC. This benefit was limited to patients with non-mutated exon 2 of the KRAS gene.
The results of clinical trials also suggest that anti-EGFR therapy restores the antitumor activity of the cytostatic irinotecan in refractory patients. The presented phase II study is the first direct comparison of the efficacy and safety of the combination of irinotecan with cetuximab or panitumumab in patients with mCRC refractory to 5-fluorouracil, irinotecan, and oxaliplatin-based chemotherapy.
Study Methodology
From August 2011 to September 2014, 121 patients with non-mutated exon 2 of the KRAS gene who had previously been treated with 5-fluorouracil, irinotecan, or oxaliplatin-based chemotherapy were enrolled in the study. Patients were randomized in a 1:1 ratio to receive either 150 mg/m2 irinotecan every 2 weeks combined with 6 mg/kg panitumumab every 2 weeks, or cetuximab in an initial dose of 400 mg/m2 followed by 250 mg/m2 weekly. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety profile.
Results
87% of patients in the study had primary tumors on the left side of the colon or in the rectum, 63% had liver metastases, and 97% had been treated with bevacizumab prior to the study.
The median PFS in the panitumumab group was 5.42 months, while it was 4.27 months in the cetuximab group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.44−0.94; p < 0.001 for non-inferiority and p = 0.058 for superiority). The median OS was 14.85 months for patients treated with panitumumab and 11.53 months for those on cetuximab (HR 0.66; 95% CI 0.44−1.00; p = 0.050 for superiority).
The safety profile of the treatment was consistent with previous observations. Hematologic toxicities were more common in the cetuximab arm, while hypomagnesemia was more frequently observed in the panitumumab arm. The incidence of skin toxicities was comparable between the two groups, and infusion reactions were very rare.
Conclusion
In patients with chemotherapy-refractory mCRC, panitumumab in combination with irinotecan achieved comparable efficacy in terms of progression-free survival as cetuximab in the same combination.
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Source: Sakai D., Taniguchi H., Sugimoto N. et al. Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G). Eur J Cancer 2020; 135: 11–21, doi: 10.1016/j.ejca.2020.04.014.
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