Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping

Background: Approved treatments for colorectal cancer (CRC) patients pretreated with two lines of therapy are of limited efficacy. Anti-epidermal growth factor receptor (EGFR) re-challenge might represent an option in RAS wild-type tumours. This study aimed to evaluate the efficacy of anti-EGFR re-c...

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Main Authors: J. Sgouros, A. Eliades, K. Papadopoulou, N. Korfiatis, D. Papamichael, E. Fountzilas, E. Tsolaki, A. Achilleos, K. Tsangaras, C. Loizides, G. Oikonomopoulos, T. Makatsoris, E. Kypri, M. Ioannides, G. Koumbaris, G. Fountzilas, P.C. Patsalis, G. Pentheroudakis
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:ESMO Gastrointestinal Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949819824000815
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author J. Sgouros
A. Eliades
K. Papadopoulou
N. Korfiatis
D. Papamichael
E. Fountzilas
E. Tsolaki
A. Achilleos
K. Tsangaras
C. Loizides
G. Oikonomopoulos
T. Makatsoris
E. Kypri
M. Ioannides
G. Koumbaris
G. Fountzilas
P.C. Patsalis
G. Pentheroudakis
author_facet J. Sgouros
A. Eliades
K. Papadopoulou
N. Korfiatis
D. Papamichael
E. Fountzilas
E. Tsolaki
A. Achilleos
K. Tsangaras
C. Loizides
G. Oikonomopoulos
T. Makatsoris
E. Kypri
M. Ioannides
G. Koumbaris
G. Fountzilas
P.C. Patsalis
G. Pentheroudakis
author_sort J. Sgouros
collection DOAJ
description Background: Approved treatments for colorectal cancer (CRC) patients pretreated with two lines of therapy are of limited efficacy. Anti-epidermal growth factor receptor (EGFR) re-challenge might represent an option in RAS wild-type tumours. This study aimed to evaluate the efficacy of anti-EGFR re-challenge strategies (panitumumab/chemotherapy). Materials and methods: RAS wild-type metastatic CRC patients following first-line chemotherapy + anti-EGFR agent and second-line chemotherapy ± anti-vascular endothelial growth factor agent were eligible. Panitumumab with irinotecan or oxaliplatin-based chemotherapy was used. The primary objective was response rate (RR). Secondary objectives were safety, progression-free survival and overall survival. Next-generation sequencing-based genotyping in archived tissue and plasma was carried out to identify prognostic factors. Results: The study closed prematurely, due to poor accrual, with 23 patients included. Most patients had primary tumours in the left colon/rectum, and the liver was the most common metastatic site. Treatment modifications were required in 74% of patients due to side-effects primarily, neutropenia and acneiform rash. One patient died from hepatic failure. The objective RR in the intention-to-treat population was 13%, and the disease control rate (DCR) was 52%. Forty-eight percent of patients tested via liquid biopsy had RAS mutations before re-challenge with panitumumab despite a median interval from previous anti-EGFR therapy of 12 months. Control of disease did not correlate with the results of liquid biopsy. RR and DCR in patients without RAS mutations in liquid biopsies were 18.2% and 54.5%, respectively. Conclusion: Panitumumab/chemotherapy as an anti-EGFR re-challenge strategy had modest activity in our patient cohort.
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spelling doaj-art-b4985d13ea404b9daa8d42b705efa7ae2025-08-20T03:42:37ZengElsevierESMO Gastrointestinal Oncology2949-81982025-03-01710012010.1016/j.esmogo.2024.100120Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotypingJ. Sgouros0A. Eliades1K. Papadopoulou2N. Korfiatis3D. Papamichael4E. Fountzilas5E. Tsolaki6A. Achilleos7K. Tsangaras8C. Loizides9G. Oikonomopoulos10T. Makatsoris11E. Kypri12M. Ioannides13G. Koumbaris14G. Fountzilas15P.C. Patsalis16G. Pentheroudakis17Department of Medical Oncology, Agii Anargiri Cancer Center and Genaral Hospital, Athens, Greece; Correspondence to: Dr Joseph Sgouros, Medical Oncology Department, Agii Anargiri Cancer Center and General Hospital, N.Kifisia, Athens, Greece 14564. Tel: +30-21-03-50-12-77Medicover Genetics, Nicosia, CyprusLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, GreeceDepartment of Informatics, Ionian University, Corfu, GreeceBank of Cyprus Oncology Center, Nicosia, CyprusDepartment of Medical Oncology, St Luke’s Clinic, Thessaloniki, Greece; European University Cyprus, Engomi, CyprusLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, GreeceMedicover Genetics, Nicosia, CyprusMedicover Genetics, Nicosia, Cyprus; Department of Life and Health Sciences, University of Nicosia, Nicosia, CyprusMedicover Genetics, Nicosia, CyprusSecond Department of Medical Oncology, Metropolitan Hospital, Piraeus, GreeceDivision of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, GreeceMedicover Genetics, Nicosia, CyprusMedicover Genetics, Nicosia, CyprusMedicover Genetics, Nicosia, CyprusAristotle University of Thessaloniki, Thessaloniki, GreeceMedicover Genetics, Nicosia, Cyprus; Department of Human Genetics, School of Medicine, University of Nicosia Medical School, Nicosia, CyprusDepartment of Medical Oncology, Medical School, University of Ioannina, Ioannina, GreeceBackground: Approved treatments for colorectal cancer (CRC) patients pretreated with two lines of therapy are of limited efficacy. Anti-epidermal growth factor receptor (EGFR) re-challenge might represent an option in RAS wild-type tumours. This study aimed to evaluate the efficacy of anti-EGFR re-challenge strategies (panitumumab/chemotherapy). Materials and methods: RAS wild-type metastatic CRC patients following first-line chemotherapy + anti-EGFR agent and second-line chemotherapy ± anti-vascular endothelial growth factor agent were eligible. Panitumumab with irinotecan or oxaliplatin-based chemotherapy was used. The primary objective was response rate (RR). Secondary objectives were safety, progression-free survival and overall survival. Next-generation sequencing-based genotyping in archived tissue and plasma was carried out to identify prognostic factors. Results: The study closed prematurely, due to poor accrual, with 23 patients included. Most patients had primary tumours in the left colon/rectum, and the liver was the most common metastatic site. Treatment modifications were required in 74% of patients due to side-effects primarily, neutropenia and acneiform rash. One patient died from hepatic failure. The objective RR in the intention-to-treat population was 13%, and the disease control rate (DCR) was 52%. Forty-eight percent of patients tested via liquid biopsy had RAS mutations before re-challenge with panitumumab despite a median interval from previous anti-EGFR therapy of 12 months. Control of disease did not correlate with the results of liquid biopsy. RR and DCR in patients without RAS mutations in liquid biopsies were 18.2% and 54.5%, respectively. Conclusion: Panitumumab/chemotherapy as an anti-EGFR re-challenge strategy had modest activity in our patient cohort.http://www.sciencedirect.com/science/article/pii/S2949819824000815colorectal cancerRAS wild typeanti-EGFR re-challengepanitumumab
spellingShingle J. Sgouros
A. Eliades
K. Papadopoulou
N. Korfiatis
D. Papamichael
E. Fountzilas
E. Tsolaki
A. Achilleos
K. Tsangaras
C. Loizides
G. Oikonomopoulos
T. Makatsoris
E. Kypri
M. Ioannides
G. Koumbaris
G. Fountzilas
P.C. Patsalis
G. Pentheroudakis
Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
ESMO Gastrointestinal Oncology
colorectal cancer
RAS wild type
anti-EGFR re-challenge
panitumumab
title Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
title_full Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
title_fullStr Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
title_full_unstemmed Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
title_short Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping
title_sort anti egfr re challenge with chemotherapy in ras wild type advanced colorectal cancer a repeat study efficacy and correlations with tissue and plasma genotyping
topic colorectal cancer
RAS wild type
anti-EGFR re-challenge
panitumumab
url http://www.sciencedirect.com/science/article/pii/S2949819824000815
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