Thavaneswaran S
Cetuximab and panitumumab are monoclonal antibodies directed against the Epidermal Growth Factor Receptor (EGFR) which are now standard treatments for RAS Wild Type (WT) metastatic Colorectal Cancer (CRC), with efficacy in all lines of therapy. The evolution of the use of the EGFR-Inhibitors (EGFR-I) is the landmark journey of the application of a predictive marker and its translation into clinical utility. Here we describe how the evaluation of EGFR-I in patients with the resistant biomarker, i.e., RAS mutant, led to clinical suspicion that the G13D subset of mutated tumours may in fact be an exception. The hypothesis, raised from preclinical data, then retrospective analysis of trial outcomes, was subsequently prospectively tested by our group in a randomised clinical trial (RCT; the ICECREAM study) which unfortunately did not reveal that this particular mutation conferred sensitivity to EGFRI. The investigation of EGFR-I in KRAS G13D mutated metastatic CRC is a good example of the ability of international collaboration to perform RCTs even in rare molecular subtypes, as well as confirming the role of prospective clinical trial evaluation of hypotheses raised by unplanned subgroup analyses.
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