The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5-34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9-43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4-44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS (p = 0.24) or progression-free survival (p = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR.

Biomedical Center Faculty of Medicine in Pilsen Charles University 32300 Pilsen Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital Videnska 800 14059 Prague Czech Republic

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital in Pilsen Charles University alej Svobody 80 32300 Pilsen Czech Republic

Faculté de Médecine Paris Centre Université de Paris 75006 Paris France

Faculté de Médecine Université Paris Saclay 94043 Le Kremlin Bicêtre France

Gastroenterology and Digestive Oncology Department Cochin Hospital AP HP 27 rue du Faubourg Saint Jacques 75014 Paris France

Hôpital Bicêtre AP HP 78 rue du General Leclerc 94043 Le Kremlin Bicêtre France

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Netroufalky 5 62500 Brno Czech Republic

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