Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.
Humans
Amphiregulin
/ metabolism
Epiregulin
/ metabolism
Cetuximab
/ therapeutic use
Panitumumab
Retrospective Studies
Colorectal Neoplasms
/ pathology
Artificial Intelligence
Intercellular Signaling Peptides and Proteins
/ metabolism
Colonic Neoplasms
/ drug therapy
Rectal Neoplasms
/ drug therapy
Proto-Oncogene Proteins p21(ras)
/ metabolism
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
ErbB Receptors
/ metabolism
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
13 10 2023
13 10 2023
Historique:
received:
24
03
2023
revised:
31
05
2023
accepted:
22
06
2023
medline:
8
11
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56-0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50-0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice. See related commentary by Randon and Pietrantonio, p. 4021.
Identifiants
pubmed: 37363997
pii: 727521
doi: 10.1158/1078-0432.CCR-23-0859
pmc: PMC10570673
doi:
Substances chimiques
Amphiregulin
0
Epiregulin
0
Cetuximab
PQX0D8J21J
Panitumumab
6A901E312A
Intercellular Signaling Peptides and Proteins
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Editorial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4153-4165Subventions
Organisme : Medical Research Council
ID : MR/N005872/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
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