Possibilities and substantiation of re‑treatment with anti‑EGFR drugs for pre‑treated RAS wild‑type advanced colorectal cancers

03/2021

MUDr. Zdeněk Linke

Onkologická klinika 2. LF UK a FN v Motole, Praha

SUMMARY

Initial failure of epidermal growth factor receptor (EGFR) inhibitor therapy in advanced RAS wild-type (wt) colorectal cancers may not necessarily mean its permanent and definitive ineffectiveness. It is possible to re-apply anti-EGFR treatment after previous disease progression (rechallenge), or after a previous interruption for reasons other than progression (reintroduction), or sequence, resp. rotation between two different EGFR blockers (sequence) or an attempt to overcome the resistance of anti-EGFR treatment by increasing its dose (escalation) or the possibility of continuous EGFR blockade. Clinical data are available to demonstrate that, especially after discontinuation of primary anti-EGFR therapy and subsequent differential therapy, sensitivity to this therapy does return. This is by changing the proportion of EGFR positive RAS wt tumor cells. This occurs during another, intervening therapy, which is based on an effect different from EGFR blockade. However, a prerequisite for the effect of reintroduced anti-EGFR treatment is its effectiveness during its previous, primary application.

Key words

advanced RAS wild-type colorectal cancer, cetuximab, panitumumab, rechallenge, reintro- duction, sequence, dose intensification, strategy of permanent EGFR blockade