The most frequent grade @ or higher regorafenib-related adverse events were hand-foot skin reaction ( @ -LSB- @ % -RSB- of @ patients in the regorafenib group vs none in the placebo group ) , hypertension ( @ -LSB- @ % -RSB- vs two -LSB- @ % -RSB- of @ patients in the placebo group ) , hyperbilirubinaemia ( nine -LSB- @ % -RSB- vs one -LSB- @ % -RSB- ) , hypophosphataemia ( nine -LSB- @ % -RSB- vs none ) , alanine aminotransferase concentration increases ( nine -LSB- @ % -RSB- vs none ) , aspartate aminotransferase concentration increases ( eight -LSB- @ % -RSB- vs none ) , lipase concentration increases ( six -LSB- @ % -RSB- vs one -LSB- @ % -RSB- ) , and maculopapular rash ( six -LSB- @ % -RSB- vs none ) .