KRAS mutational status does not seem to influence the outcome of maintenance treatment with erlotinib in patients with metastatic colorectal cancer (mCRC), according to a new study published online ahead of print in the journal Annals of Oncology.1

Because maintenance treatment with bevacizumab, a VEGF angiogenesis inhibitor, with or without erlotinib, an EGFR tyrosine kinase inhibitor, has only a modest effect following induction chemotherapy in patients with mCRC, researchers sought to evaluate whether KRAS mutational status impacts the efficacy of erlotinib treatment.

For the study, researchers enrolled 233 treatment-naïve patients (median age = 64 years) with mCRC. Patients received 18 weeks of induction chemotherapy with XELOX/FOLFOX or XELIRI/FOLFIRI plus bevacizumab and the 138 without disease progression were then eligible for maintenance therapy.

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KRAS wild-type patients were randomly assigned to receive bevacizumab with or without erlotinib, while KRAS mutated patients were randomly assigned to receive bevacizumab or metronomic capecitabine.

Results showed that median progression-free survival was not significantly different between KRAS wild type patients that received bevacizumab alone and those that received bevacizumab plus erlotinib (HR, 1.03; 95% CI, 0.70–1.50; P=.867).

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The 3-month progression-free survival rate was 64.7% and 63.6%, respectively, and 75% and 66.7% in KRAS mutated patients who received bevacizumab and those who received metronomic capecitabine, respectively.

In regard to safety, KRAS wild type patients, particularly those who also received erlotinib, experienced more frequent grade 3 and 4 toxicities during maintenance therapy.

“Metronomic capecitabine warrants further investigation in maintenance strategies, given our explorative results,” the authors concluded.


  1. Hagman H, Frödin J-E, Berglund Å, et al. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial [published online ahead of print October 19, 2015]. Ann Oncol. doi: 10.1093/annonc/mdv490.