Anti-EGFR-based maintenance versus stop and go in patients with left-sided, non-MSI-H, RAS/BRAF-wt metastatic...

Doublet chemotherapy plus an anti- epidermal growth factor receptor (EGFR) agent is a standard of care in patients with left-sided, microsatellite stable, RAS/BRAF wild-type (wt) mCRC. No conclusive evidence is available to guide treatment de-escalation, but several randomized clinical trials investigated either maintenance or intermittent treatment schedules (stop and go).

We performed an individual patient data pooled analysis of four multicenter, randomized phase II trials (PanaMa, Valentino, PRODIGE-28 TIME, IMPROVE). Only patients with left-sided, non-microsatellite instability-high, RAS/BRAFV600E-wt who started the protocol-planned post-induction treatment were included and stratified into three treatment groups: maintenance with 5-fluorouracil/leucovorin (5-FU/LV) plus anti-EGFR, maintenance with anti-EGFR alone, or stop and go. The primary endpoint was overall survival (OS) with stop and go versus 5-FU/LV plus anti-EGFR maintenance. Secondary endpoints were progression-free survival (PFS) and time to failure of strategy (TFS) with stop and go versus 5-FU/LV plus anti-EGFR; and OS, PFS, and TFS with stop and go versus anti-EGFR alone.

A total of 378 molecularly selected left-sided patients were included. Overall, 166, 109, and 103 patients received maintenance with 5-FU/LV plus anti-EGFR, anti-EGFR alone, or stop and go, respectively. No significant differences in OS were reported between stop and go versus 5-FU/LV plus anti-EGFR maintenance [median 26.3 versus 29.7 months, hazard ratio (HR) 1.24, P = 0.530], or stop and go compared with anti-EGFR alone (median 26.3 versus 30.1 months, HR 1.39, P = 0.165). PFS was significantly shorter with stop and go, while TFS was comparable between stop and go compared with both maintenance schedules.

This pooled analysis of candidates considered optimal for initial anti-EGFR-based therapy supports both stop and go and maintenance as de-intensification strategies to consider in shared decision making. Adequately powered phase III studies are advocated to compare the two strategies.