Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation

Abstract

Background: Bevacizumab plus chemotherapy prolongs progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although there is strong evidence to suggest that the mutational status of the K-ras oncogene has a role as a predictive factor for activity in patients treated with cetuximab and panitumumab, few data have been obtained in patients treated with bevacizumab. We conducted an additional retrospective analysis to investigate the prognostic value of K-ras mutation relative to mCRC first-line treatment with bevacizumab.

Materials and methods: A total of 108 patients were retrospectively reviewed. K-ras status was assessed in the overall population by sequencing. Statistical association for PFS and OS was analyzed using the Kaplan-Meier method, and the prognostic role of K-ras was determined using the logrank test.

Results: Median PFS was 10 months both for patients with wild-type (WT) K-ras and mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92; P=0.70). A further analysis was carried out in the two groups according to metastatic sites. No statistically significant difference in terms of PFS and OS was demonstrated between WT K-ras and MT K-ras with liver metastases only and in those with extrahepatic disease.

Conclusion: Although further study is required, our results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.

Keywords: K-ras; bevacizumab; extrahepatic disease; liver metastases; metastatic colorectal cancer; prognostic factor.

Figure 1

(A) Progression-free survival according to K-ras status; (B) overall survival according to K-ras status. Abbreviations: WT, wild type; MT, mutated; mPFS, median progression-free survival; mOS, median overall survival; HR, hazard ratio; CI, confidence interval.

Figure 2

(A) Progression-free survival according to metastatic site; (B) overall survival according to metastatic site. Abbreviations: mPFS, median progression-free survival; mOS, median overall survival; HR, hazard ratio; CI, confidence interval.

Figure 3

(A) Progression-free survival according to K-ras status in liver-only metastasis patients; (B) overall survival according to K-ras status in liver-only metastasis patients. Abbreviations: WT, wild type; MT, mutated; mPFS, median progression-free survival; mOS, median overall survival; HR, hazard ratio; CI, confidence interval.

Figure 4

(A) Progression-free survival according to K-ras status in extrahepatic metastatic patients; (B) overall survival according to K-ras status in extrahepatic metastatic patients. Abbreviations: WT, wild type; MT, mutated; mPFS, median progression-free survival; mOS, median overall survival; HR, hazard ratio; CI, confidence interval.