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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

The survival of patients with metastatic colorectal cancer (mCRC) has been improved over the years and now reaches 30–40 months. However, few therapeutic options are available after failure of first- and second-line treatments. In fact, prognosis of chemo-refractory mCRC remains poor. Therefore, new therapeutic strategies are needed. Emerging evidence suggest that retreatment with epidermal growth factor (EGFR) inhibitors after a treatment break, in patients that obtained a clinical benefit by previous anti-EGFR, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that after a “treatment holiday” EGFR resistant cancer cells decay, restoring the sensibility to EGFR blockade. In this review we analyze the current knowledge of retreatment with EGFR inhibitors, examine the role of novel biomarkers that can guide the appropriate selection of patients. Finally, we discuss future perspectives and on-going clinical trials.

Abstract

The prognosis of patients with metastatic colorectal cancer (mCRC) who progressed to the first and the second lines of treatment is poor. Thus, new therapeutic strategies are needed. During the last years, emerging evidence suggests that retreatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) in the third line of mCRC patients, that have previously obtained clinical benefit by first-line therapy with anti-EGFR MAbs plus chemotherapy, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that, after disease progression to first line EGFR-based therapy, a treatment break from anti-EGFR drugs results in RAS mutant cancer cell decay, restoring the sensitivity of cancer cells to cetuximab and panitumumab. In fact, rechallenge treatment with anti-EGFR drugs has shown promising clinical activity, particularly in patients with plasma RAS and BRAF wild type circulating tumor DNA, as defined by liquid biopsy analysis at baseline treatment. The aim of this review is to analyze the current knowledge on rechallenge and to investigate the role of novel biomarkers that can guide the appropriate selection of patients that could benefit from this therapeutic strategy. Finally, we discuss on-going trials and future perspectives.

Details

Title
Biomarker-Guided Anti-EGFR Rechallenge Therapy in Metastatic Colorectal Cancer
Author
Ciardiello, Davide 1 ; Martini, Giulia 2   VIAFID ORCID Logo  ; Famiglietti, Vincenzo 2 ; Napolitano, Stefania 2 ; De Falco, Vincenzo 2   VIAFID ORCID Logo  ; Troiani, Teresa 2 ; Latiano, Tiziana Pia 3 ; Ros, Javier 4   VIAFID ORCID Logo  ; Fernandez, Elena Elez 5 ; Vitiello, Pietro Paolo 6   VIAFID ORCID Logo  ; Maiello, Evaristo 3   VIAFID ORCID Logo  ; Ciardiello, Fortunato 2 ; Martinelli, Erika 2 

 Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy; [email protected] (D.C.); [email protected] (G.M.); [email protected] (V.F.); [email protected] (S.N.); [email protected] (V.D.F.); [email protected] (T.T.); [email protected] (J.R.); [email protected] (F.C.); Oncologia Medica, IRCCS Foundation Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; [email protected] (T.P.L.); [email protected] (E.M.) 
 Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy; [email protected] (D.C.); [email protected] (G.M.); [email protected] (V.F.); [email protected] (S.N.); [email protected] (V.D.F.); [email protected] (T.T.); [email protected] (J.R.); [email protected] (F.C.) 
 Oncologia Medica, IRCCS Foundation Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy; [email protected] (T.P.L.); [email protected] (E.M.) 
 Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy; [email protected] (D.C.); [email protected] (G.M.); [email protected] (V.F.); [email protected] (S.N.); [email protected] (V.D.F.); [email protected] (T.T.); [email protected] (J.R.); [email protected] (F.C.); Department of Medical Oncology, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain; [email protected] 
 Department of Medical Oncology, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain; [email protected] 
 Dipartimento di Oncologia, Istituto per la Ricerca sul Cancro (IRCC), Università di Torino, 10060 Candiolo, Italy; [email protected] 
First page
1941
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2547626782
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.