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The association of doublet chemotherapy (FOLFOX and FOLFIRI) and anti-EGFR moAbs (panitumumab or cetuximab) is a standard option for the first-line treatment of unresectable RAS and BRAF wt metastatic colorectal cancer (mCRC) patients, especially with left-sided primary tumour.
Rechallange with anti-EGFR moAbs is a promising strategy in patients who previously achieved benefit from a first-line anti-EGFR-based treatment and not bearing RAS mutation on circulating tumour DNA (ctDNA) at the rechallenge baseline.
Based on results from phase III trials, regorafenib, a multi-kinase inhibitor, is approved for treatment of refractory mCRC patients.
Drawing from these considerations, we designed the present phase II randomized study of panitumumab followed at progression by regorafenib (arm A) versus the reverse sequence (arm B) in RAS and BRAF wt mCRC patients without RAS/BRAF mutations at ctDNA analysis.

Selection criteria

– RAS and BRAF wt metastatic colorectal cancer (mCRC) patients;
– previous treatment for metastatic disease with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic monoclonal antibody (bevacizumab or aflibercept);
– previous first-line anti-EGFR-containing therapy producing at least a partial response or a stable disease ≥ 6 months;
– RAS and BRAF wt status of circulating tumour DNA (ctDNA) at screening (central laboratory assessment by means of IdyllaTM ctKRAS-NRAS-BRAF Mutation Test, Biocartis, Inc.);
– adequate hematopoietic, liver and renal function.


The primary objective is to compare the efficacy in terms of OS of panitumumab followed after disease progression by regorafenib (arm A) versus the reverse sequence (arm B) in RAS/BRAF wt ctDNA chemorefractory mCRC patients with previous benefit from first-line anti-EGFR-based treatment.

Participating centers