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 mCRC patients, especially with left-sided primary tumour.
In RAS wt mCRC patients refractory to chemotherapy and anti-EGFR naive, the standard
treatment sequence is an anti-EGFR-based therapy (panitumumab or cetuximab +/- irinotecan)
followed by regorafenib.
In a phase II randomized Japanese study named REVERCE, a higher OS was reported in favour of
an experimental strategy of regorafenib followed at progression by cetuximab +/- irinotecan
compared with the reverse standard sequence in chemorefractory and anti-EGFR-naïve, RAS wt
However, the limitations of the REVERCE study (phase II trial with a premature conclusion for
poor accrual) do not allow us to draw definitive conclusions. In addition, nowadays, patients
candidates to an anti-EGFR-based treatment, receive anti-EGFRMoAbs in earlier lines of
therapy thus affecting the translation of these results in the current clinical practice.
Retrospective analyses and a phase II single-arm trial showed promising activity of anti-EGFR
rechallenge in patients who previously achieved benefit from a first-line anti- EGFR-based
treatment and not bearing RAS mutation on ct-DNA at the rechallenge baseline.
Based on these considerations, the Investigators designed the present phase II randomized
study of panitumumab followed at progression by regorafenib versus the reverse sequence in
RAS and BRAF wt mCRC patients with the following characteristics:
previous treatment with, or not considered candidates for, fluoropyrimidine,
oxaliplatin, irinotecan and an anti-angiogenic agent (bevacizumab or aflibercept);
RECIST response or stable disease lasting at least 6 months to a previous first-line
RAS and BRAF wt ct-DNA at the time of screening. The aim of this study is to compare the
two sequences in a Caucasian population of patients candidates to anti-EGFR rechallenge.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.