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
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
Related
- Chemotherapy outcomes in human epidermal growth factor receptor 2-low, hormone receptor-positive metastatic breast cancer: Insights from the French multicenter ESME database.
- Durable partial response with low-dose, intermittent nivolumab in combination with gemcitabine for high PD-L1 metastatic triple-negative breast cancer: a case report
- Case Report: Prolonged survival with short-course triplet induction and dual maintenance in recurrent/metastatic cervical cancer
- Observation versus maintenance immunotherapy after PD-1-induced clinical complete response in dMMR/MSI-H colorectal cancer managed non-operatively: a multicenter cohort study.
- Association between primary-site surgery and overall survival in non-metastatic and metastatic colorectal cancer: a population-based study using the Surveillance, Epidemiology, and End Results database
BibTeX
@article{raimondi2026toxicityovertime,
title = {{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}},
author = {Alessandra Raimondi and Gabriele Tinè and Valerie Boige and Alexej Ballhausen and Sophie Gourgou and Arndt Stahler and Giovanni Randon and Paolo Manca and Emilie Brument and Annabel Helga Sophie Alig and Federica Morano and Michele Prisciandaro and Margherita Ambrosini and Roberta Fazio and Yiyi Zhu and Rosalba Miceli and Olivier Bouche and Dominik Paul Modest and Filippo Pietrantonio},
journal = {JNCI Journal of the National Cancer Institute},
year = {2026},
month = may,
doi = {10.1093/jnci/djag160},
url = {https://doi.org/10.1093/jnci/djag160},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Alessandra Raimondi
AU - Gabriele Tinè
AU - Valerie Boige
AU - Alexej Ballhausen
AU - Sophie Gourgou
AU - Arndt Stahler
AU - Giovanni Randon
AU - Paolo Manca
AU - Emilie Brument
AU - Annabel Helga Sophie Alig
AU - Federica Morano
AU - Michele Prisciandaro
AU - Margherita Ambrosini
AU - Roberta Fazio
AU - Yiyi Zhu
AU - Rosalba Miceli
AU - Olivier Bouche
AU - Dominik Paul Modest
AU - Filippo Pietrantonio
PY - 2026
DA - 2026/05/22
JO - JNCI Journal of the National Cancer Institute
DO - 10.1093/jnci/djag160
UR - https://doi.org/10.1093/jnci/djag160
AB - 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
SN - 0027-8874
SN - 1460-2105
ER -