Associations between AI-assisted tumor amphiregulin and epiregulin IHC and outcomes from anti-EGFR therapy in the routine management of metastatic colorectal cancer.


Williams, Christopher JM, Elliott, Faye, Sapanara, Nancy, Aghaei, Faranak, Zhang, Liping, Muranyi, Andrea, Yan, Dongyao, Bai, Isaac, Zhao, Zuo, Shires, Michael et al (show 44 more authors) (2023) Associations between AI-assisted tumor amphiregulin and epiregulin IHC and outcomes from anti-EGFR therapy in the routine management of metastatic colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 29 (20). CCR-23-0859-CCR-23-0859.

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Abstract

<h4>Purpose</h4>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 immunohistochemistry (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.<h4>Experimental design</h4>Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival FFPE 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).<h4>Results</h4>494 of 541 patients (91.3%) had adequate tissue for analysis. 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% CI, 0.56-0.95; p=0.02) and OS (median: 16.4 vs 8.9 months; HR 0.66 [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.<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: Humans, Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms, Intercellular Signaling Peptides and Proteins, Antineoplastic Combined Chemotherapy Protocols, Retrospective Studies, Artificial Intelligence, Proto-Oncogene Proteins p21(ras), Amphiregulin, ErbB Receptors, Epiregulin, Cetuximab, Panitumumab
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 27 Sep 2023 10:47
Last Modified: 18 Nov 2023 03:45
DOI: 10.1158/1078-0432.ccr-23-0859
Open Access URL: https://doi.org/10.1158/1078-0432.CCR-23-0859
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3173113
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