Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone

ten Hoorn, Sanne, Sommeijer, Dirkje W., Elliott, Faye, Fisher, David, de Back, Tim R., Trinh, Anne, Koens, Lianne, Maughan, Tim, Seligmann, Jenny, Seymour, Matthew T., Quirke, Phil, Adams, Richard ORCID: https://orcid.org/0000-0003-3915-7243, Richman, Susan D., Punt, Cornelis J. A. and Vermeulen, Louis 2021. Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone. British Journal of Cancer 125 , pp. 1080-1088. 10.1038/s41416-021-01477-9

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Abstract

Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0007-0920
Date of First Compliant Deposit:	15 July 2021
Date of Acceptance:	30 June 2021
Last Modified:	09 May 2023 18:47
URI:	https://orca.cardiff.ac.uk/id/eprint/142550

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