Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years. (March 2022)

• Record Type: Journal Article
• Authors: Papamichael, Demetris; Lopes, Guilherme S.; Olswold, Curt L.; Douillard, Jean-Yves; Adams, Richard A.; 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; Shi, Qian
• Is Part Of: European journal of cancer. Volume 163(2022)
• Page Start: 1
• Page End: 15
• Publication Date: 2022-03
• Subjects: Colorectal cancer -- Older patients -- Anti-EGFR -- Cetuximab -- Panitumumab; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.12.007
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: Older patients with colorectal cancer are under-represented in clinical trials. Investigated effect of age in patients treated with chemotherapy and anti-EGFR agents. No significant difference in the risk for G3+ toxicity between over and under 70s. Comparable efficacy outcomes for younger and older patients receiving anti-EGFR agents.