Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years

Papamichael, Demetris, Lopes, Guilherme S., Olswold, Curt L., Douillard, Jean-Yves, Adams, Richard A. ORCID: https://orcid.org/0000-0003-3915-7243, Maughan, Timothy S., Van Cutsem, Eric, 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. European Journal of Cancer 163 , pp. 1-15. 10.1016/j.ejca.2021.12.007

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Abstract

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. 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. 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. Conclusions Older (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	European School of Oncology (ESO)
ISSN:	0959-8049
Date of Acceptance:	1 December 2021
Last Modified:	10 Nov 2022 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/147028

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