Updated analysis: A retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer—HGCSG1401.

Abstract

778 Background: The CORRECT trial revealed the safety and efficacy of regorafenib (REG) for patients (pts) with colorectal cancer including Japanese. REG was approved in Japan in March 2013. However, there are few studies exploring the efficacy and safety of REG in a large number of patients, particularly in daily practice. Methods: We analyzed 173 pts who received REG from May 2013 in the multi-institutional retrospective study (HGCSG1401). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients’ characteristics were as follows; male/female 98/75, median age 66 (range 29-87), ECOG PS (0/1/2/3) 58/96/18/1, KRAS Exon2 wild/mutant 98/74 (1 patient ; KRAS Exon2 status was not tested). The initial starting dose was 160 mg (n = 145, 83.8%), 120mg (n = 22, 12.7%), and 80mg (n = 6, 3.5%) respectively. Dose reductions were required in 73 pts (42.2%); 38 pts (22.0%) discontinued therapy due to AEs. The common ≥ grade 3 AEs ( ≥ 15%) were palmar-plantar erythrodysesthesia syndrome (n = 48; 27.7%), hypertension (n = 34; 19.7%), proteinuria (n = 24; 19.2%) and AST increased (n = 24; 13.9%). RR and disease control rate (DCR) were 1.3% and 29.6%, respectively. Median PFS and median survival time (MST) were 2.1 and 6.3 months. In an analysis on relationship between ECOG PS (PS 0-1 vs. PS 2-3) and efficacy, median PFS was 2.3 vs. 1.2 months (HR 3.598, p < 0.001), and MST was 7.0 vs. 2.1 months (HR 4.751, p < 0.001). Conclusions: The efficacy of REG in pts with PS 0–1 was similar to the previous report; however, REG was not effective in patients with PS 2–3. In adverse events, hypertension and liver dysfunction were expressed more frequently than previously reported. We will continue the analysis of the factors associated with liver dysfunction and prognostic/predictive factors.