The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients….Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0).

...•Male or female patients > 18 years •Histological or cytological documentation of adenocarcinoma of the colon or rectum •Genetic diagnosis of RAS(hot spot mutations KRAS codon 2-3-4 and NRAS at least codon 2-3) wild type tumor . ...

...Descriptive summary of demographics characteristics`Descriptive summary of Stage of disease`Descriptive summary of Eastern Cooperative Oncology Group (ECOG) performance status`Descriptive summary of Primary tumor status`Descriptive summary of Number of metastatic`Descriptive summary of Site of metastasis`Descriptive summary of K-RAS mutation status and N-RAS mutation status`Descriptive summary of Line of therapy (LOT) for regorafenib`Descriptive summary of Prior adjuvant treatment`Descriptive summary of Treatments prior to index date, overall and by LOT`Descriptive summary of Pre-existing comorbidities...

...Percentage of patients with mutated BRAF status at index`Percentage of patients with mutated KRAS status at index.`...

...Proportion of patients with a DoT to Stivarga of more than 4 months versus total study sample`ECOG: Eastern Cooperative Oncology Group`ECOG performance status (0, 1)`Rectum, Left-sided colon, Right-sided colon, Colon and rectum, Transverse, Unknown (in colon)`Primary site of disease`Tumor resection (yes, no, unknown)`Lung, Liver, Bone, Extraregional nodes, Peritoneum, Multiple, Unknown`Specific site of metastasis`KRAS mutation (yes, no, unknown)`RAS mutation (yes, no, unknown)`BRAF mutation (yes, no, unknown)...

The mOS of Pts received regorafenib monotherapy (R, n = 376), regorafenib plus PD-1 inhibitor (R+I, n = 161)...While the median PFS were 3.8, 5.4, 4.6 and 4.8 months, respectively (p = 0.4944). In multivariate analysis, treatment with R+I (HR = 0.712, 95%CI 0.521-0.973; p = 0.0330) and ECOG PS (HR = 0.400, 95%CI 0.232-0,690; p = 0.0010) were the only significant factors for superior mOS. Univariate analysis in subgroups demonstrated longer OS as well as PFS in KRAS mutated or antiangiogenesis therapy naïve Pts in R+I group than those in R group...The combination of regorafenib and PD-1 inhibitor was commonly adopted as the later-line treatment in mCRC patients in real-world practice and seemed to have a prolonged overall survival than regorafenib alone.

At data cut-off, median treatment duration and median follow-up were 4.6 mo. (range: 2.3; 10) and 13.4 mo. (range: 3.8; 18.0), respectively. One DLT (a grade 3 hypokalaemia related to grade 2 diarrhoea) occurred at DL 2. MTD was not reached at DL 3 (REGO 160 mg/day). The most common grade ≥3 TRAE per patient were grade 3 neutropenia (n = 1), grade 4 neutropenia (n = 1), grade 3 neuropathy (n = 2) and grade 3 diarrhoea (n = 7). Dose reductions/discontinuations due to grade ≥3 TRAE were necessary in 12/13 (92%) pts. The ORR was 62% (95% CI 32%-86%) and median PFS was 9.1 mo (range: 3.1; 15.4). Full-dose FOLFIRINOX plus full-dose REGO (160mg/day, days 4 to 10) can be administered safely. Due to the manageable toxicity profile and the promising efficacy observed in the dose-escalation stage...

We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator....Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC....

Compared with control cells, proliferation and migration of all the tumor cell lines were inhibited by clinically effective concentrations of regorafenib (5–8 μM), irrespective of their KRAS and BRAF mutation status (Fig. 1).