1. Biomarker-Guided Anti-Egfr Rechallenge Therapy in Metastatic Colorectal Cancer
- Author
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Stefania Napolitano, Vincenzo Famiglietti, Vincenzo De Falco, J. Ros, Elena Elez Fernandez, Pietro Paolo Vitiello, Fortunato Ciardiello, Evaristo Maiello, Tiziana Latiano, Teresa Troiani, Giulia Martini, Davide Ciardiello, Erika Martinelli, Institut Català de la Salut, [Ciardiello D] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. Oncologia Medica, Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy. [Martini G, Famiglietti V, Napolitano S, De Falco V, Troiani T] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. [Ros J] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain. [Elez Fernandez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Ciardiello, D., Martini, G., Famiglietti, V., Napolitano, S., De Falco, V., Troiani, T., Latiano, T. P., Ros, J., Fernandez, E. E., Vitiello, P. P., Maiello, E., Ciardiello, F., and Martinelli, E.
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,rechallenge ,anti-EGFR monoclonal antibodies ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Review ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES] ,Growth factor receptor ,Metàstasi ,Anti-EGFR monoclonal antibodie ,Internal medicine ,Recte - Càncer - Tractament ,Medicine ,Panitumumab ,Còlon - Càncer -Tractament ,Other subheadings::/therapeutic use [Other subheadings] ,Liquid biopsy ,RC254-282 ,Chemotherapy ,Cetuximab ,business.industry ,Otros calificadores::/uso terapéutico [Otros calificadores] ,metastatic colorectal cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,medicine.disease ,neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES] ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Biomarker (medicine) ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,business ,medicine.drug - 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.
- Published
- 2021