Comparable survival outcome with anti-EGFR therapy in any treatment line in left-sided metastatic colorectal cancer

Abstract

Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) are the standard first-line treatment in RAS wild-type (RASwt) left-sided metastatic colorectal cancer (mCRC), but the benefit of later treatment is unclear. This study aimed to assess whether the timing of anti-EGFR mAb therapy influences survival outcomes in this population. Methods: We conducted a retrospective study in patients diagnosed with RASwt mCRC who received anti-EGFR mAb in all treatment lines between 2008 and 2023. The impact of line of anti-EGFR mAb on progression-free survival (PFS) and overall survival (OS) was determined using the Kaplan-Meier method and compared with the log-rank test. Results: Of 300 patients with RASwt left-sided mCRC patients receiving anti-EGFR mAb, 32% of the patients (98 of 300) were treated in the first-line, while 15% and 51% were treated in the second- and third-to later-line, respectively. Anti-vascular growth factors were used in 34% of patients. Median follow-up time was 30.4 months. Patients receiving anti-EGFR mAb in the first-line setting exhibited a significantly longest median PFS [11.87 months; 95% confidence interval (CI): 5.28–18.46; P<0.001]. The median PFS in the second- and third- to later-line settings were 5.75 months (95% CI: 4.16–7.35; P<0.001), and 5.06 months (95% CI: 3.86–6.27; P<0.001), respectively. There were no significant differences in terms of OS among treatment lines (P=0.29). Conclusions: While earlier line use confers longer PFS, OS remains similar regardless of the timing of anti-EGFR therapy. These findings support the introduction of anti-EGFR agents at any line when feasible, highlighting that ensuring access may be more important than timing in treatment sequencing.