OBJECTIVES: Effectiveness of regorafenib, an oral multi-kinase inhibitor, in metastatic colorectal cancer patients (mCRC) was based on the results achieved in two international, phase III randomized clinical trials (RCTs). However, due to restricted nature and controlled settings of the eligibility criteria of RCTs, data from these trials may not fully represent the efficacy and safety profiles of regorafenib in real-world (RW) clinical practice. Therefore, overall aim of this study was to review RW studies on the use of REG in ≥ 3 line-treatment for mCRC patients refractory to standard therapies.

METHODS: A targeted literature review was performed using PubMed to search RW studies of mCRC patients treated in ≥ 3-line with regorafenib monotherapy. The search was limited to English language, last conducted on 12 September 2022 and with a 10-year filter. Endpoints such as median-overall survival (OS), -progression-free survival (PFS), -treatment duration (TD) and treatment-related adverse events (TRAE) were analyzed.

RESULTS: Targeted literature search revealed 15 RW studies (Japan and China [n=3 each], Global and France [n=2 each], and Germany, Czech Republic, United States, Canada, Hong Kong [n=1 each]). In terms of study design, most (n=8) of the studies were prospective, followed by retrospective (n=4), ambispective (n=2) and claims database (n=1). Median OS, PFS and TD was 7.5, 2.7 and 2.4 months, respectively. Grade ≥3 TRAEs, i.e., hand-foot skin reaction (21%), fatigue (21%), hypertension (17%), hypophosphatemia (15%), weight loss (11%), anemia (9%), hyperbilirubinemia (9%), and diarrhea (4%), occurred in 37% patients assigned regorafenib which led to either dose reduction or treatment discontinuation in 65% and 27% of patients, respectively.

CONCLUSIONS: The results of our research demonstrated similar or slightly better efficacy of regorafenib treatment to that reported in RCTs, but at the expense of toxicity. Future studies are warranted to identify potential biomarkers/parameters that will help tailor regorafenib therapy in minimizing toxicity.