Options and rationale for reinstituting anti-EGFR therapy in pretreated RAS wild-type advanced colorectal carcinomas
Abstract
Failure of anti-EGFR therapy in advanced RAS wild-type colorectal carcinoma at the initial lines of treatment may not necessarily mean its permanent and definitive inefficacy. One option is retreatment with anti-EGFR based therapies after previous progression (i. e., rechallenge).
Another option is to reinitiate anti-EGFR treatment after previous discontinuation for a reason other than progression (i. e., reintroduction). Alternatively, sequential treatment can be used, i. e., switching between various anti-EGFR agents.
A last option is to reinstitute anti-EGFR treatment in an effort to overcome the resistance of anti-EGFR therapy by dose escalation or continuous EGFR blockade. There are clinical data demonstrating that, particularly after discontinuation of primary anti-EGFR treatment and subsequent different treatment, restoration of sensitivity to the anti-EGFR therapy does occur.
This is done by a change in the proportion of EGFR-positive, RAS wild-type tumour cells. This occurs during another, intercalated therapy, which is the basis of an effect different from EGFR blockade.
However, for the reinstituted anti-EGFR therapy to be effective, efficacy during its previous, i. e., primary, administration is a prerequisite.