CORRECT trial has shown a survival benefit for regorafenib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies. We evaluated survival, safety and prognostic subgroups in patients treated with regorafenib in a real-life setting. Retrospective, multicenter, observational study of patients (pts) with mCRC treated with Regorafenib (REG) after failure to standard therapies as part of routine clinical practice at 7 hospitals from the Galician Research Group on Digestive Tumors (GITuD). We recorded 130 pts treated with REG between September 2013 to December 2019. Median age was 63 years (range 27-79), 94.6% ECOG PS0-1, 55.4% RASmt and 1.5% BRAFmt, 18% time since initial diagnosis 3 metastatic locations and 75% liver metastases. Prior therapy included a median of 3 lines of treatment (range 2-8), including Trifluridine/Tipiracil in 29.2% of pts. FAS-CORRECT 0-3/4-5/6+ were 32.6%/35.7%/38.1% and Tabernero subgroups BPC/GPC/PPC were 20%/42.3%/37.3%. Median of REG cycles was 3 (range 1-18 cycles). With a median follow up of 23.4 months, median OS was 6.7 months (95% CI, 6.1-7.3 months) with 12- month OS rate 20.8% and median PFS was 2.9 months (95% CI, 2.7-3.0 months) with 6-month PFS rate 14.6%. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 4.6% and 25.4%, respectively. The most common grade 3-4 toxicities were asthenia (12.3%), hyperbilirubinaemia (6.4%), hypertension (3.9%) and hand-foot skin reaction (3.9%). This toxicity was managed with dose reduction in 39.2 % of cases. OS FAS-CORRECT 0-3/4-5/6+ were 9.2 vs. 6.9 vs. 5.3 m (p=0.138) and OS Tabernero subgroups BPC/GPC/PPC were 10.5 vs. 6.9 vs. 5.2 m (p=0.022). DCR FAS-CORRECT 0-3/4-5/6+ were 37.5% vs. 28.5% vs. 22.9% (p=0.121) and DCR Tabernero subgroups BPC/GPC/PPC were 48% vs. 21.1% vs. 24.4% (p=0.004). OS and PFS observed in our serie were consistent with the CORRECT trial, although in our routine clinical practice they were slightly higher. FAST-CORRECT and, especially, Tabernero's prognostic subgroups identify patients who may benefit from long-term Regorafenib treatment.

After regorafenib (REG) was approved due to a survival benefit in refractory metastatic colorectal cancer (mCRC), some predictive markers such as the FAS and FAS-CORRECT scores have been proposed to improve patient selection. We have explored the survival and safety outcomes of REG in a real-life setting and tried to find and validate predictive markers. We conducted a retrospective, multicentre, observational study of pts with mCRC treated with REG after failure to standard therapies as part of routine clinical practice at seven hospitals from the Galician Research Group on Digestive Tumors (GITuD). We recorded 130 pts treated with REG between September 2013 to December 2019. Median age was 63 years (range 27-79 years), 65.4% male, ECOG PS0/1/2 19.2/75.4/4.6%, 45.4% left-sided location, 78.5% low grade, 55.4% RASmt and 1.5% BRAFmt, 58.5% synchronous presentation, 76.2% primary tumor resection, 32.3% >3 metastatic locations and 75% liver metastases. Median prior lines of treatment were 3 (range 2-8) including TAS-102 in 29.2% of pts. Initial dose: 53.1% pts full standard dose, 14.6% dose level -1, 16.9% dose level -2. 15.4% pts used a dose-escalation strategy (ReDOS strategy). Dose selection 60 (OS 5.2 vs 9.1; p 85 (OS 6.4 vs 9.0; p= 0.016) achieved prognostic significance. Median of weeks until reimbursement approval was 3.1 weeks. Patients who had to wait longer to start treatment had lower OS (5.2 vs 7.8; p=0.006) despite having similar clinical characteristics. The results of our series corroborate that REG offers and modest survival benefit in all patients with refractory mCRC, which can be significant in selected patients. Although we have not been able to validate the FAS and FAS-correct algorithms, our results suggest that they could be useful and some important parameters that reflect disease burden are confirmed to be predictors of poor prognosis. Finally, we have identified for the first time in our study, that delay of treatment due to reimbursement reasons is an independent prognostic factor.