During the European Society for Medical Oncology Meeting (ESMO) 2014, in Madrid, Spain, the results from two different studies evaluating the use of anti-EGFR or anti-VEGF treatments in first-line RAS wild type metastatic colorectal cancer patients were presented.
Dr. Heinz-Josef Lenz of the Division Of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, presented results from the CALGB/SWOG 80405 study, a Phase III trial of FOLFIRI or mFOLFOX6 with bevacizumab or cetuximab for patients with expanded RAS analyses in untreated metastatic adenocarcinoma of the colon or rectum.
Earlier results from this trial had already demonstrated that the combination of FOLFIRI/cetuximab and mFOLFOX6/bevacizumab were similar regarding overall survival in patients with previously untreated KRAS wild type metastatic colorectal cancer. However, these results were obtained in the original trial setting, which included unselected patients with metastatic colorectal cancer who received treatment according to physician-selected chemotherapy (FOLFIRI or mFOLFOX6) and were randomised to cetuximab, bevacizumab or both.
The researchers then refined their study design by including only patients with wild type KRAS tumours (codon 12 and 13), observing that the median overall survival was pushed beyond 30 months. Nonetheless, no significant differences in overall survival were observed between cetuximab (32 months) and bevacizumab (31.2 months) in combination with chemotherapy.
In another study, presented by Dr. Sebastian Stintzing of the University of Munich, Department of Hematology and Oncology, results from the FIRE-3 study, comparing first-line therapy with FOLFIRI plus either cetuximab or bevacizumab and designed to include only KRAS wild-type patients, were presented.
The results showed that FOLFIRI plus cetuximab induced a significantly higher overall response rate, a greater rate of early tumour shrinkage and an increased depth of response, compared to FOLFIRI plus bevacizumab.
A radiological review was performed to evaluate tumour response, with results demonstrating an overall response rate of 66.5% in the cetuximab arm and 55.6% in the bevacizumab arm for the KRAS exon 2 wild type populations.
Because metastatic colorectal cancer is a highly heterogenous disease, one of its subsets is extremely dependent on EGFR signaling. As such, KRAS and NRAS testing should be preformed to identify if a patient will benefit from treatment with anti-EGFR monoclonal antibodies.
According to Dr. Fortunato Ciardiello, one of the discussants in the ESMO session, “All metastatic colorectal cancer patients should have extended RAS testing before first-line treatment choice to offer them all available therapeutic opportunities”. Furthermore, he believes that FOLFIRI or FOLFOX with an anti-EGFR antibody should be the first-line choice if tumour shrinkage is a relevant therapeutic goal.