The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster development of resistance when sensitive cells are eradicated and when the RAS-mutant anti-EGFR resistant clones become predominant.
The characteristics of low-level RAS mutant tumors would be:
* Objective response rate (ORR) high (reflecting the sensitive clone) * Progression-free survival (PFS) short (reflecting the more rapid outgrowth of RAS mutant clones)
Histologically confirmed, UICC stage IV metastatic adenocarcinoma of the colon or rectum
Primarily non-resectable metastases or surgical resection refused by the patient
RAS mutation determined by the local pathology
Age ≥18
Previous chemotherapy for metastatic disease with the exception of one cycle of FOLFIRI (e.g. while waiting for the result of RAS mutation frequency).
Patients planned to be treated with FOLFOX or another oxaliplatin-based regimen as first-line treatment
Primarily resectable metastases and the patient agrees to resection
Grade III or IV heart failure (NYHA classification)