Efficacy and safety of regorafenib compared to TAS-102 for refractory metastatic colorectal cancer.

e15010 Background: Recent studies have shown Regorafenib (R) and TAS-102 (TAS) to be superior to placebo (P) in refractory metastatic colorectal cancer (mCRC). However, no studies have directly compared R with TAS. We aimed to compare the efficacy and safety of R compared with TAS using indirect comparison methods. Methods: We conducted a systematic review using PubMed, Medline, Embase, Scopus and Cochrane database to identify published and unpublished studies up to November 2015 for randomized controlled trials (RCTs) for patients with mCRC, involving Regorafenib or TAS-102. Data including overall survival (OS), progression-free survival (PFS) and toxicity (Tox) were extracted. Pairwise direct meta-analyses (R vs. P and TAS vs. P) and indirect comparison (R vs. TAS) using network meta-analyses methods (R package “netmeta”) to preserve randomization were performed. Results: 914 citations were initially identified among which 3 RCTs fulfilled eligibility criteria (CORRECT, CONCUR and TAS-102) involving 1,764 patients (R: 641, TAS: 534, P: 589). Subgroups of patients (1,659) who had not received prior R or TAS were used to performed meta-analyses for efficacy. Results of efficacy and toxicity are shown in table. Conclusions: In this indirect comparison, R and TAS appeared to have similar efficacy. However, R appears to have more toxicity compared to TAS. Post-approval real world data focusing on the comparative toxicity of R and TAS is warranted. R vs. P (direct) TAS vs. P (direct) R vs. TAS (indirect) HR/OR 95% CI HR/OR 95% CI HR/OR 95% CI OS 0.71 0.60-0.83 0.69 0.57-0.83 1.02 0.80-1.32 PFS 0.45 0.39-0.52 0.47 0.39-0.56 0.96 0.76-1.21 Tox (all grades) 10.43 6.70-15.53 4.24 1.88-9.57 2.46 0.99-6.08 Tox (grades≥3) 7.22 5.08-10.26 2.12 1.57-2.87 3.40 2.14-5.42