1. Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone
- Author
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Dirkje W. Sommeijer, Matthew T. Seymour, Lianne Koens, Cornelis J. A. Punt, Sanne ten Hoorn, David Fisher, Tim Maughan, Louis Vermeulen, Faye Elliott, Anne Trinh, Phil Quirke, Susan D. Richman, Jenny F. Seligmann, Tim R. de Back, Richard Adams, Center of Experimental and Molecular Medicine, Graduate School, CCA - Cancer biology and immunology, Amsterdam Gastroenterology Endocrinology Metabolism, Oncology, and Pathology
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Cetuximab ,Irinotecan ,Article ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Chemotherapy ,Humans ,Panitumumab ,Neoplasm Metastasis ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,Clinical Trials as Topic ,business.industry ,Middle Aged ,medicine.disease ,Survival Analysis ,Oxaliplatin ,ErbB Receptors ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,ras Proteins ,Immunohistochemistry ,Female ,Colorectal Neoplasms ,business ,medicine.drug - 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 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.
- Published
- 2021