Regorafenib in Metastatic Colorectal Cancer and Advanced Soft Tissue Sarcomas

Abstract

Oncologists face multiple challenges when treating patients with cancer, especially if patients are elderly or if they experience adverse events (AEs). Several presentations at the American Society of Clinical Oncology (ASCO) 2016 meeting focussed on overcoming these challenges with regorafenib, an oral multikinase inhibitor approved for treating refractory metastatic colorectal cancer (mCRC), and gastrointestinal stromal tumours (GIST). A retrospective analysis of the Phase IIIb CONSIGN study in patients with mCRC reported while most AEs were similar between age groups, when compared to the younger subgroup, the patients in the older subgroups had a higher incidence of Grade ≥3 fatigue and a lower incidence Grade ≥3 hand-foot syndrome (HFS), while other AEs were similar between age groups. Thus, patient age should not be considered a barrier to regorafenib use. This age analysis also highlighted the key role of dose modification in the management of regorafenib-related AEs. Another tactic for AE management is to utilise specific treatments targeted to the AE of interest. Interim analysis of a Phase II study demonstrated that prophylactic dexamethasone had promising effects in reducing regorafenib-related fatigue and HFS in patients with mCRC. In an ongoing Phase II study, ReDOS, both regorafenib dose-escalation and use of clobetasol propionate to actively manage regorafenib-induced HFS are under investigation. Finally, the success of regorafenib in treating GIST, the most common soft tissue sarcoma (STS), has been extended to patients with other STS. In REGOSARC, a Phase II study, regorafenib significantly prolonged progression-free survival (PFS) in patients with non-adipocytic STS, with an AE profile similar to that seen in mCRC and GIST. These presentations offer insights into the practical management of patients treated with regorafenib.