, Volume 1, Issue 4, pp 253-257

Colorectal cancer

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Summary

Results of this year's ASCO saw significant steps towards an individualized therapy based upon genetic testing of KRAS. Numerous studies demonstrated that the effectiveness of epidermal growth factor receptor (EGFR) inhibitors is completely dependent upon KRAS mutational status. This led to the approval of EGFR inhibitor therapy in first and late-line therapy only in KRAS wildtype patients at least in Europe. In a retrospective analysis of the CRYSTAL trial Patients with KRAS wild-type tumours who received cetuximab were found to have a 1.2-month longer PFS and a 16% higher response rate compared with those who received chemotherapy alone. Patients with KRAS-mutant tumours who received cetuximab had 0.5-month shorter PFS and a 4% lower response rate than did patients with KRAS-mutant tumours who received chemotherapy alone. In the chemotherapy-only arm, KRAS status did not affect PFS or chemotherapy response. The same pattern of response was observed in the OPUS trial. Patients with KRAS wild-type tumours treated with chemotherapy and cetuximab had a 0.5-month longer PFS and a 24% higher response rate; for those with KRAS mutant tumours (99 patients, 42%), the addition of cetuximab was associated with a 3.1-month shorter PFS and a 16% lower response rate. In the chemotherapy-only arm, KRAS status did not affect PFS or chemotherapy response. The CAIRO 2 trial evaluated the combination of capecitabine (Xeloda), oxaliplatin (Eloxatin) and bevacizumab (Avastin) with or without the addition of cetuximab in patients with metastatic colorectal cancer. Overall, the addition of cetuximab resulted in an inferior PFS (9.6 vs 10.7 months) but did not affect response rate (44% in either arm) or overall survival (OS; 20.4 months). For KRAS wild-type patients (305, 61%), the addition of cetuximab did not affect PFS (10.5 vs 10.7 months). Antibody therapy combining cetuximab and bevacizumab has no clear benefit for patients receiving first-line chemotherapy plus bevacizumab and should not be used outside the context of a clinical trial. Further important topics in this year's ASCO included updates on the use, safety and efficacy of Bevacizumab in the first-line treatment of metastatic CRC as well as in the perioperative setting. Results of the NSABC-07 trials strengthened the role of oxaliplatin in the adjuvant treatment of stage III CRC.