Improving Patient Outcomes with Regorafenib for Metastatic Colorectal Cancer - Patient Selection, Dosing, Patient Education, Prophylaxis, and Management of Adverse Events

Abstract

Regorafenib is the first tyrosine kinase inhibitor approved for metastatic colorectal cancer. In 2 phase III trials, regorafenib significantly improved progression-free and overall survival in patients who had been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy, and, if (K)RAS wild type, an anti-epidermal growth factor receptor therapy. Its safety profile is in line with other multikinase and/or tyrosine kinase inhibitors approved for different indications. Commonly reported adverse events specifically associated with regorafenib include hand-foot skin reaction and hypertension, whereas others such as fatigue, diarrhea, and liver dysfunction may occur during both targeted and cytotoxic treatments. These adverse events frequently occur within the first cycles of treatment, are transient, and decrease in incidence over time. Patient selection, education, and management, as well as close communication between oncologists or trained nurses and patients, are essential for prevention and mitigation of treatment toxicity as is rapid implementation of dose modifications and temporary discontinuations. Effective management of adverse events enables patients who are responding to stay on treatment for a substantial period of time and thereby receive the full benefit of regorafenib therapy. This review aims to provide guidance around prophylaxis and management of regorafenib-associated adverse events.

Treatment Outcomes of Metastatic Colorectal Cancer Patients Treated with Regorafenib as Third-Line Setting-A Multicenter Study

“…Approximately 13.04% of patients discontinued treatment due to toxicity. The median number of treatment cycles was three (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The most common toxicities of any grade were hand-foot skin reaction (HFSR), fatigue, diarrhea, hypertension, mucositis and thrombocytopenia.…”

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report

“…Prolonged treatment with regorafenib in our patient may be partly attributable to the mild AEs. Severe AEs associated with regorafenib are known to occur during the first and second courses of treatment [ 10 ]. Although our patient had a deteriorated health condition at the beginning of this treatment, regorafenib did not lead to severe AEs.…”

Practical considerations in the use of regorafenib in metastatic colorectal cancer

“…37,42,44 If HFSR occurs, management should be proactive and include reinforcement of preventive measures, topical creams, pain relief as necessary, and dose interruption/reduction (see Figure 1 and Table 3 for details). 37,42,44 Hypertension occurs relatively frequently during regorafenib treatment, but it is not cumulative, and provided it is treated appropriately, it has negligible impact on patients' QoL. 43 Pre-existing hypertension should be well controlled before the start of regorafenib treatment and blood pressure should be measured frequently during treatment, at least weekly in the first two cycles and then at the start of subsequent cycles.…”

“…1,19,37,[47][48][49] A lower starting dose Adapted from published sources. 37,[42][43][44] ACE, angiotensin-converting enzyme; AE, adverse event; HFSR, hand-foot skin reaction.…”