Work

Toxicity-over-time analysis of anti–epidermal growth factor receptor–based maintenance vs intermittent in left-sided RAS and BRAF wild-type metastatic colorectal cancer

Year: 2026

Type: article

Abstract: BACKGROUND: Doublet chemotherapy plus anti-epidermal growth factor receptor (EGFR) is a standard of care in left-sided, microsatellite stable RAS and BRAF wild-type metastatic colorectal cancer. Guidelines recommend treatment de-escalation after achieving disease control with induction. Maintenance and intermittent strategies were investigated but not directly compared. METHODS: We performed an individual patient data pooled analysis of 3 randomized phase II trials (PanaMa, Valentino, PRODIGE-28 TIME) focused on toxicity analysis. Only patients with left-sided, nonmicrosatellite instability high RAS and BRAF V600E wild type who started protocol-planned postinduction were included and stratified into 3 treatment groups: 5-fluorouracil and leucovorin plus anti-EGFR maintenance, anti-EGFR alone, or intermittent. Longitudinal toxicity data were collected and analyzed according to literature-based approach (toxicity over time), incorporating dimension of time into adverse event assessment and analyzing individual and groups of adverse events comparing treatment groups. RESULTS: Overall, 327 patients were included: 166, 109, and 52 patients received anti-EGFR plus 5-fluorouracil and leucovorin maintenance, anti-EGFR alone, and intermittent strategy, respectively. Mean adverse event grades for chemotherapy-related toxicity showed different longitudinal patterns. Mean grades in intermittent strategy were lower in early cycles and increased later, and higher values were reported for combination maintenance. Considering anti-EGFR-related skin toxicity, the mean adverse event grade was constantly lower for intermittent strategy compared with maintenance groups. Overall, grades 3 and 4 adverse events were more represented in maintenance groups vs intermittent strategy, although the predominant grade was 1 across cycles for all groups. CONCLUSIONS: In our individual patient data analysis, indirectly comparing 3 clinical trials, intermittent strategy showed lower anti-EGFR skin-related toxicity vs maintenance. Shared decision making, considering patient and tumor features and treatment tolerability, may allow defining optimal de-intensification strategy.+*+9.

Source: JNCI Journal of the National Cancer Institute

DOI: 10.1093/jnci/djag160