Table A6.

Dose Modification or Delay for Hypertension at Any Time

Hypertension Grade	Management
1	Consider increased blood pressure monitoring
2	Begin antihypertensive therapy and continue regorafenib
3	Hold regorafenib until symptoms resolve and diastolic BP < 100 mmHg; also treat patient with antihypertensive medications (if previously normal blood pressure) or increase current antihypertensive medications or add additional antihypertensive medications; when regorafenib is restarted, reduce by one dose level*
	If diastolic BP is not controlled (< 100 mmHg) with the addition of new or more intensive therapy, reduce another dose level†
4	Discontinue study drug

Abbreviation: BP, blood pressure.

^*Patients requiring a delay of > 4 weeks were removed from protocol. If blood pressure remained controlled for at least one full cycle, dose re-escalation was permitted at discretion of investigator.

^†Dose reductions below dose level − 3 were not allowed; if dose reductions below dose level − 3 were required, study drug administration was discontinued.