Panitumumab (EGFR mAb) drives ctDNA “High→Low” conversions that track ~51–61mo OS in 1L mCRC

ctDNA dynamics were analyzed in PARADIGM (Phase 3; mFOLFOX6 + panitumumab vs mFOLFOX6 + bevacizumab) using paired baseline and post-treatment plasma from 556 patients with mCRC, stratified into High/Mid/Low ctDNA by Gaussian mixture modeling (NCT02394795; NCT02394834). Baseline ctDNA was strongly prognostic for OS (Low: 50.7mo; Mid: 34.1mo; High: 27.8mo), and post-treatment ctDNA further refined risk: patients converting to Low ctDNA had the best survival even from a High baseline (High→Low OS 50.9mo), while persistently high ctDNA did worst (High→High OS 23.3mo). In the High-baseline subset, more patients reached Low ctDNA with panitumumab vs bevacizumab (19.1% vs 10.8%, p=0.053) alongside more discontinuations after curative resection (e.g., High→Low: 62.1% vs 43.8%), with directionally better OS/PTS for panitumumab (High→Low OS 61.0 vs 43.1mo; HR 0.49), consistent with PARADIGM’s established OS advantage for panitumumab over bevacizumab in left-sided RAS WT disease (~37.9 vs 34.3mo) despite similar imaging-based PFS.