Comparison of efficacy and safety of regorafenib and anti-EGFR targeted therapy in metastatic colorectal cancer: A retrospective study

Aim. To compare the efficacy of regorafenib and the combination of chemotherapy (CT) with anti-EGFR (cetuximab/panitumumab) in the third-line treatment of metastatic colorectal cancer (mCRC).

Materials and methods. A retrospective analysis of a prospective database of patients with mCRC from two clinics in the Russian Federation was conducted. Overall survival was considered the primary efficacy criterion. Additional criteria were progression-free survival (PFS), objective effect (OE), and incidence of toxicity. No statistical hypothesis was assumed. Statistical analysis was performed using SPSS (IBM SPPS Statistics v. 20).

Results. The database identified 51 patients with morphologically confirmed left-sided mCRC with wild-type RAS and BRAF genes who received more than two lines of antitumor drug therapy from 2010 to 2021, one of which included anti-EGFR antibodies in the third and subsequent lines of treatment. Thirty patients who received regorafenib in the third line and 21 patients who received CT in combination with anti-EGFR in the third line were selected, of which 7 patients had a history of anti-EGFR use, and 14 patients received anti-EGFR for the first time. The median overall survival from the third line initiation date in the CT group in combination with anti-EGFR was numerically higher (21 months, CI 9.0–32.9 months) than in the regorafenib group (10 months, CI 2.4–17.5 months); p=0.1 by log-rank test (Mantel–Cox test); p=0.2 by Breslow–Wilcoxon test; p=0.3 (Tarone–Ware test). PFS was also higher in the anti-EGFR CT group (6 months, CI 3.8–8.2 months) than in the regorafenib group (3 months, CI 1.2–4.7 months); p=0.05 according to Breslow–Wilcoxon test. OE of third-line therapy was reported in 57.1% (n=12) of patients in the CT with anti-EGFR group and significantly less often in the regorafenib group – 10.3% (n=3) of patients (p=0.001). The toxicity of drug therapy of all grades in the regorafenib group was reported in 86.2% (n=25) of patients, while in the CT anti-EGFR group, it was significantly less common – in 52.4% (n=11) of patients (p=0.01).

Conclusion. Compared with regorafenib, combining CT with anti-EGFR agents in the third-line treatment of patients with left-sided mCRC with wild-type RAS and BRAF genes is associated with better PFS and the frequency of OE with significantly less toxicity.