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Updated: May 26, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Toxicity-over-time analysis of anti-EGFR-based maintenance versus stop&go in left-sided, RAS/BRAF wild-type
Alessandra Raimondi1, Gabriele Tinè2, Valerie Boige3
1Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Background:
Doublet chemotherapy plus anti-EGFR is a standard of care in left-sided, microsatellite stable, RAS/BRAF wt (wt) mCRC. Guidelines recommend treatment de-escalation after achieving disease control with induction. Maintenance and intermittent (stop&go) strategies were investigated but not directly compared.
Methods:
We performed an individual patient data pooled analysis of three randomized phase II trials (PanaMa, Valentino, PRODIGE-28 TIME), focused on toxicity analysis. Only patients with left-sided, non-MSI-H, RAS/BRAF V600E wt who started protocol-planned post-induction were included and stratified into three treatment groups: 5-FU/LV plus anti-EGFR maintenance, anti-EGFR alone, stop&go. Longitudinal toxicity data were collected and analyzed according to literature-based approach (Toxicity over Time; ToxT), incorporating dimension of time into adverse event (AE) assessment and analyzing individual and groups of AEs comparing treatment groups.
Results:
Overall, 327 patients were included: 166, 109 and 52 patients received anti-EGFR plus 5-FU/LV maintenance, anti-EGFR alone and stop&go, respectively. Mean AE grades for chemotherapy-related toxicity showed different longitudinal patterns. Mean Grades in stop&go were lower in early cycles and increased later, higher values were reported for combination maintenance. Considering anti-EGFR-related skin toxicity, the mean AE grade was constantly lower for stop&go compared to maintenance groups. Overall, grade 3/4 AEs were more represented in maintenance groups versus stop&go, although the predominant grade was 1 across cycles for all groups.
Conclusions:
In our IPD analysis, indirectly comparing three clinical trials, stop&go showed lower anti-EGFR skin-related toxicity versus maintenance. Shared decision-making, considering patient and tumor features and treatment tolerability, may allow defining optimal de-intensification strategy.
