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

Abstract

BackgroundBevacizumab 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 methodsA 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.ResultsMedian 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.ConclusionAlthough 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.

Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view

“…Within the subgroup of patients with metastatic disease limited to one distant organ we did not observed difference in clinical outcome with regard to hepatic or extrahepatic (including pulmonary) involvement. Interestingly, together with Rossi et al [ 19 ], we observe trend toward longer both PFS and OS in patients with extrahepatic disease and KRAS mutation than in wtKRAS subgroup when treated with bevacizumab plus chemotherapy. Apart from this fact, we and others [ 20 - 22 ] have reported that KRAS mutation in colorectal cancer itself is associated with pulmonary metastasis.…”

Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study

“…It is worth noting that we found a median PFS of 10.5 and 10.1 months in wt and mut, respectively, which is in accordance with the median interval of 10 months reported in both KRAS groups in a recent retrospective study assessing the prognostic impact of these mutations in patients with mCRC (64% wt and 36% mut) receiving first-line bevacizumab. 27…”

“…It is worth noting that we found a median PFS of 10.5 and 10.1 months in wt and mut, respectively, which is in accordance with the median interval of 10 months reported in both KRAS groups in a recent retrospective study assessing the prognostic impact of these mutations in patients with mCRC (64% wt and 36% mut) receiving first-line bevacizumab. 27 When patients classified by KRAS status were further subgrouped based on the reason for treatment discontinuation, few differences were found, which mostly reflected those of the whole cohort.…”

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

“…The incidence is 30 times lower in India, South America, and Africa. In Japan, the incidence is increasing gradually, reaching similar rates in the UK, presumably as a result of changes in lifestyle and diet 2–7…”