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Papamichael, Demetris; Lopes, Guilherme S.; Olswold, Curt L.; Douillard, Jean-Yves; Adams, Richard A.; Maughan, Timothy S.; Cutsem, Eric van; Venook, Alan P.; Lenz, Heinz-Josef; Heinemann, Volker; Kaplan, Richard; Bokemeyer, Carsten; Chibaudel, Benoist; Grothey, Axel; Yoshino, Takayuki; Zalcberg, John; De Gramont, Aimery and Shi, Qian (2022): Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer = 70 years. In: European Journal of Cancer, Vol. 163: pp. 1-15

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Purpose: Colorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients.& nbsp;Methods: Patients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included. The prognostic and predictive effects of age were investigated. Progression-free and overall survival (OS) were evaluated between age groups (>= 70 vs < 70) for DC + anti-EGFR. In addition, outcomes were compared between DC+/-anti-EGFR within age groups in three trials with a DC alone arm. Subsequently, the same analysis was conducted for left-sided tumours. Adverse events grade >= 3 (G3+) were compared between age groups.& nbsp;Results: Older (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months;hazard ratio (HR) = 1.20 [0.96-1.49];p = 0.107) but inferior OS (21.3 vs 26.3;HR = 1.36 [1.08-1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3;HR = 0.82 [0.70-0.95];p = 0.008) and PFS (11.2 vs 8.9;HR = 0.70 [0.60-0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6;HR [95% confidence interval {CI}] = 0.77 [0.58-1.04];p = 0.092) and PFS (9.1 vs 8.7;HR [95% CI] = 0.85[0.63-1.15];p = 0.287). In left-sided 'only' tumours, the following outcomes for older (vs younger) patients were observed. For DC + anti-EGFR, PFS 9 versus 11.2 months;HR1.10 (95% CI 0.83-1.46);p = 0.52, OS 25.6 vs 30.3 HR 1.32 (95% CI 0.97 -1.79), p = 0.086. For DC + anti-EGFR (vs DC alone), PFS and OS for younger patients were 11.9 vs 9.2 months HR 0.60 (95% CI 0.47-0.78) p < 0.001 and 24.1 versus 23.3 months HR 0.84 (95% CI 0.67-1.04), respectively. For older patients, PFS and OS were 13.1 versus 8.5 months, HR 0.51 (95% CI, 0.28-0.93), P = 0.027 and 26.3 versus 16.5 months HR 0.49 (95% CI, 0.28-0.85), respectively. There was no significant difference in toxicity among different age groups.& nbsp;Conclusions: Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.& nbsp;(C) 2021 Elsevier Ltd. All rights reserved.

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