Toxicity profile of fruquintinib (Fruq) versus regorafenib (Rego) in refractory metastatic colorectal cancer (mCRC).

Abstract

e15608 Background: Anti-VEGF TKIs are a cornerstone in the management of refractory mCRC. Fruq is FDA-approved for refractory mCRC that has similar efficacy outcomes to Rego. Fruq’s target selectivity might offer a safer adverse events profile than Rego. This study aims to review the current literature on the treatment-related adverse events (TRAEs) of Rego and Fruq in clinical trial settings. Methods: We searched PubMed, Scopus, ClinicalTrials.gov and CENTRAL databases for clinical trials that included patients with refractory mCRC treated with Rego or Fruq. Studies with combinational therapies like immune checkpoint inhibitors and chemotherapy were included. We excluded studies with patients treated with combinational targeted therapies. Our main study outcomes were the occurrence of any-grade TRAEs and G3/4 TRAEs. Secondary outcomes were any-grade and G3/4 hypertension (HTN), hand-foot skin reaction (HFSR), fatigue. Meta-analysis with head-to-head comparisons with placebo using risk ratio (RR) and a proportional single-arm meta analysis were conducted. Results: 41 clinical trials were included consisting of 6435 patients in total, 949 of them were treated with Fruq. Trials were classified into those containing Rego only arm (N = 22), Fruq only (N = 5), Rego & chemotherapy (N = 5), Rego & immunotherapy (N = 5), Fruq & immunotherapy (N = 4). Compared to placebo, Fruq monotherapy had a lower risk of any-grade TRAE than regorafenib monotherapy (RR: 1.27, 95% CI: 1.01 to 1.60 and RR: 1.76, 95% CI: 1.27 to 2.44) and G3/4 (RR: 1.62, 95% CI: 1.40 to 1.88 and RR: 3.83, 95% CI: 2.89 to 5.07). Fruq monotherapy showed higher rates of HTN than Rego (Table). As for Fruq & immunotherapy, 2 trials showed that 34% of the patients had G3/4 TRAE, 16% had G3/4 HTN, 13% had G3/4 HFSR, and no patients had G3/4 fatigue. Conclusions: Compared to Rego, Fruq showed a more favorable toxicity profile in all TRAEs except in HTN where Fruq had a higher risk. This review emphasizes the need for direct head-to-head comparisons between Fruq and Rego in experimental settings. TRAE Grade Rego Fruq Rego & chemotherapy Rego & immunotherapy All Any 96% 97% 99% 94% G3/4 63% 48% 57% 45% HTN Any 29% 39% 26% 25% G3/4 11% 19% 13% 10% HFSR Any 39% 25% 34% 49% G3/4 14% 10% 7% 10% Fatigue Any 39% 16% 43% 39% G3/4 8% 3% 6% 5%