Table 2.

Treatment-emergent AEs with an incidence ≥20% (safety analysis set).

	Regorafenib 72 mg/m2 with VI (CON; n = 2)		Regorafenib 72 mg/m2 with VI (SEQ; n = 6)		Regorafenib 82 mg/m2 with VI (SEQ; n = 13)		Total (N = 21)
Event, n (%)	All grades	Grade ≥3	All grades	Grade ≥3	All grades	Grade ≥3	All grades	Grade ≥3
Diarrhea	2 (100)	0	5 (83)	1 (17)	12 (92)	3 (23)	19 (90)	4 (19)
Anemia	2 (100)	0	4 (67)	1 (17)	9 (69)	6 (46)	15 (71)	7 (33)
Neutropeniaa	2 (100)	2 (100)	6 (100)	6 (100)	7 (54)	7 (54)	15 (71)	15 (71)
Abdominal pain	2 (100)	2 (100)	4 (67)	1 (17)	8 (62)	1 (8)	14 (67)	4 (19)
Pyrexia	1 (50)	0	4 (67)	0	8 (62)	1 (8)	13 (62)	1 (5)
Vomiting	2 (100)	2 (100)	3 (50)	0	8 (62)	2 (15)	13 (62)	4 (19)
Decreased appetite	2 (100)	1 (50)	5 (83)	0	5 (38)	1 (8)	12 (57)	2 (10)
Thrombocytopeniab	1 (50)	1 (50)	4 (67)	2 (33)	7 (54)	4 (31)	12 (57)	7 (33)
Nausea	1 (50)	1 (50)	3 (50)	1 (17)	6 (46)	0	10 (48)	2 (10)
ALT increased	2 (100)	2 (100)	3 (50)	2 (33)	4 (31)	1 (8)	9 (43)	5 (24)
AST increased	2 (100)	2 (100)	3 (50)	2 (33)	4 (31)	0	9 (43)	4 (19)
Dry skin	0	0	2 (33)	0	6 (46)	0	8 (38)	0
Hypokalemia	2 (100)	1 (50)	1 (17)	0	5 (38)	3 (23)	8 (38)	4 (19)
Leukopeniac	1 (50)	1 (50)	3 (50)	3 (50)	4 (31)	3 (23)	8 (38)	7 (33)
Rash	2 (100)	0	3 (50)	0	3 (23)	0	8 (38)	0
Weight decreased	1 (50)	1 (50)	2 (33)	0	5 (38)	0	8 (38)	1 (5)
GGT increased	2 (100)	1 (50)	2 (33)	1 (17)	3 (23)	0	7 (33)	2 (10)
Hypophosphatemia	2 (100)	1 (50)	2 (33)	1 (17)	3 (23)	1 (8)	7 (33)	3 (14)
Alopecia	0	0	2 (33)	0	4 (31)	0	6 (29)	0
Fatigue	2 (100)	0	2 (33)	0	2 (15)	0	6 (29)	0
Headache	1 (50)	0	2 (33)	0	2 (15)	0	5 (24)	0
Cough	1 (50)	0	2 (33)	0	2 (15)	0	5 (24)	0
Pain	0	0	1 (17)	0	4 (31)	1 (8)	5 (24)	1 (5)
Proteinuria	1 (50)	0	2 (33)	0	2 (15)	0	5 (24)	0
Constipation	1 (50)	0	1 (17)	0	2 (15)	0	4 (19)	0
TSH increased	0	0	2 (33)	0	2 (15)	0	4 (19)	0
Hypocalcemia	1 (50)	0	0	0	3 (23)	1 (8)	4 (19)	1 (5)
Epistaxis	0	0	1 (17)	0	3 (23)	0	4 (19)	0
Hypertension	0	0	2 (33)	0	2 (15)	0	4 (19)	0
Hyponatremia	1 (50)	0	1 (17)	1 (17)	2 (15)	0	4 (19)	1 (5)
Lethargy	0	0	2 (33)	0	2 (15)	0	4 (19)	0
Myalgia	0	0	2 (33)	0	2 (15)	0	4 (19)	0
Rash maculopapular	1 (50)	0	1 (17)	1 (17)	2 (15)	0	4 (19)	1 (5)
Abdominal distension	0	0	1 (17)	0	2 (15)	0	3 (14)	0
Asthenia	0	0	1 (17)	0	2 (15)	1 (8)	3 (14)	1 (5)
Blood bilirubin increased	1 (50)	0	1 (17)	0	1 (8)	0	3 (14)	0
Blood creatinine increased	0	0	0	0	3 (23)	1 (8)	3 (14)	1 (5)
Dyspepsia	1 (50)	0	1 (17)	0	1 (8)	0	3 (14)	0
Febrile neutropenia	1 (50)	1 (50)	1 (17)	1 (17)	1 (8)	1 (8)	3 (14)	3 (14)
Leukocyturia	0	0	2 (33)	0	1 (8)	0	3 (14)	0
Lymphopeniad	1 (50)	0	1 (17)	0	1 (8)	1 (8)	3 (14)	1 (5)
Pain in extremity	0	0	2 (33)	0	1 (8)	0	3 (14)	0
Pain in jaw	1 (50)	0	1 (17)	0	1 (8)	0	3 (14)	0
HFSR	0	0	3 (50)	1 (17)	0	0	3 (14)	1 (5)
Pruritus	1 (50)	0	1 (17)	0	1 (8)	0	3 (14)	0
Stomatitis	0	0	2 (33)	0	1 (8)	0	3 (14)	0
Tachycardia	0	0	0	0	3 (23)	0	3 (14)	0
Toothache	0	0	2 (33)	0	1 (8)	0	3 (14)	0
URT infection	1 (50)	0	1 (17)	0	1 (8)	0	3 (14)	0
Acute kidney injury	0	0	0	0	2 (15)	1 (8)	2 (10)	1 (5)
Bone pain	0	0	1 (17)	0	1 (8)	0	2 (10)	0
Clostridium difficile infection	0	0	2 (33)	1 (17)	0	0	2 (10)	1 (5)
Dermatitis diaper	0	0	0	0	2 (15)	0	2 (10)	0
Dizziness	0	0	2 (33)	0	0	0	2 (10)	0
Dysgeusia	1 (50)	0	0	0	1 (8)	0	2 (10)	0
Ear pain	1 (50)	0	0	0	1 (8)	0	2 (10)	0
Erythema	0	0	0	0	2 (15)	0	2 (10)	0
Glycosuria	1 (50)	0	0	0	1 (8)	0	2 (10)	0
Hyperglycemia	1 (50)	0	1 (17)	0	0	0	2 (10)	0
Hypoalbuminemia	0	0	1 (17)	0	1 (8)	0	2 (10)	0
Hypomagnesemia	0	0	0	0	2 (15)	0	2 (10)	0
Hypotension	0	0	0	0	2 (15)	2 (15)	2 (10)	2 (10)
Hypothyroidism	0	0	0	0	2 (15)	0	2 (10)	0
Insomnia	1 (50)	0	1 (17)	0	0	0	2 (10)	0
Leukocytosis	1 (50)	0	0	0	1 (8)	0	2 (10)	0
Lipase increased	0	0	1 (17)	1 (17)	1 (8)	1 (8)	2 (10)	2 (10)
Muscle spasms	0	0	0	0	2 (15)	0	2 (10)	0
Nasopharyngitis	0	0	1 (17)	0	1 (8)	0	2 (10)	0
Neck pain	0	0	2 (33)	1 (17)	0	0	2 (10)	1 (5)
Oral pain	0	0	1 (17)	0	1 (8)	0	2 (10)	0
Pain of skin	0	0	1 (17)	1 (17)	1 (8)	0	2 (10)	1 (5)
Peripheral sensory neuropathy	1 (50)	1 (50)	1 (17)	0	0	0	2 (10)	1 (5)
Prothrombin time ratio increased	0	0	2 (33)	0	0	0	2 (10)	0
Rhinorrhea	0	0	0	0	2 (15)	0	2 (10)	0
Skin hyperpigmentation	0	0	2 (33)	0	0	0	2 (10)	0
Vascular access complication	1 (50)	0	1 (17)	0	0	0	2 (10)	0

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; HFSR, hand–foot skin reaction; TSH, thyroid stimulating hormone; URT, upper respiratory tract; VI, vincristine and irinotecan; WBC, white blood cell.

^aIncluding neutrophil count decreased.

^bIncluding platelet count decreased.

^cIncluding WBC count decreased.

^dIncluding lymphocyte count decreased.