Colon Cancer Side May Influence Cetuximab Response

Colon cancer site of origin may affect progression-free survival in patients given cetuximab

medwireNews: Left-sided (LC) and right-sided colon cancer (RC) may respond differently to cetuximab therapy, suggests a study of patients with chemotherapy refractory, metastatic disease.

Among 105 LC patients with wild-type KRAS, initial analysis indicated that overall survival (OS; 10.1 vs 4.8, hazard ratio [HR]=0.49) and progression-free survival (PFS; 5.4 vs 1.8, HR=0.28) were significantly higher in those who received the Epidermal growth factor receptor (EGFR) inhibitor than those who received best supportive care.

By contrast, neither OS, nor PFS significantly differed between the 56 RC patients with wild-type KRAS who were given cetuximab or best supportive care. Nor was there any difference in PFS between LC and RC patients who received best supportive care.

Multivariate analysis confirmed that tumour site was significantly associated with PFS with cetuximab therapy but not with OS, the researchers report in the European Journal of Cancer.

“The difference seen in efficacy with cetuximab treatment should be hypothesis generating, and support increasing efforts to improve our understanding about the molecular and histological variability in right- versus left-sided colon cancer and the impact on future targeted therapy”, say Rachel Goodwin, from the University of Ottawa in Ontario, Canada, and co-authors.

The NCIC CO.17 trial included 150 patients with RC, affecting the caecum to transverse colon, and 249 patients LC between the splenic flexure and the rectosigmoid. Seventy-eight RC and 127 LC patients were randomly assigned to receive the EGFR inhibitor, while the remaining patients were given best supportive care.

RC and LC patients significantly differed on several key characteristics, with RC patients more likely to have poorly differentiated disease (24.0 vs 12.5%), mutant KRAS (40 vs 26.5%) and wild-type BRAF (74.7 vs 67.9%) but less likely to have lung or liver metastases (86.0 vs 95.2%).

“We found that metastatic cancers originating in the left colon obtained significantly more PFS benefit from treatment with cetuximab as compared to right sided colon cancers”, the researchers comment but do say that “a benefit cannot be excluded” in PFS for RC patients.

The team concludes: “In the era of personalised medicine, being able to select treatment based on right versus left-sided colon cancer may influence future drug development and allow for more effective targeted therapy among colon cancer patients.”

Reference

Brulé SY, Jonker DJ, Karapetis CS,et al. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer 2015; Advance online publication 12 May. doi:10.1016/j.ejca.2015.03.015

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015