All Cycles Name	NC/NA, %	Grade 1, %	Grade 2, %	Grade 3, %	Grade 4, %	Grade 5, %	All grades, %
White blood cell decreased	32	16	36	16	0	0	68
Neutrophil count decreased	36	7	41	16	0	0	64
Anemia	11	41	39	9	0	0	89
Platelet count decreased	52	36	7	5	0	0	48
Alanine aminotransferase increased	78	20	0	2	0	0	22
Aspartate aminotransferase increased	55	43	2	0	0	0	45
Blood bilirubin increased	73	18	2	7	0	0	27
Creatinine increased	57	43	0	0	0	0	43
Febrile neutropenia	100	0	0	0	0	0	0
Hypertension	9	14	36	41	0	0	91
Anorexia	32	36	23	9	0	0	68
Proteinuria	31	32	30	7	0	0	69
Fatigue	36	32	32	0	0	0	64
Nausea	40	39	14	7	0	0	60
Peripheral sensory neuropathy	48	48	2	2	0	0	52
Mucositis oral	70	23	7	0	0	0	30
Vomiting	77	16	7	0	0	0	23
Palmar‐plantar erythrodysesthesia syndrome	80	20	0	0	0	0	20
Diarrhea	81	14	0	5	0	0	19
Fever	82	9	7	2	0	0	18
Weight loss	82	7	9	2	0	0	18
Dry skin	84	11	5	0	0	0	16
Alopecia	86	7	7	0	0	0	14
Dysgeusia	87	11	2	0	0	0	13
Epistaxis	89	11	0	0	0	0	11
Rash acneiform	89	9	2	0	0	0	11
Thromboembolic event	96	0	0	2	2	0	4

Adverse Events Legend

Abbreviation: NC/NA, no change from baseline/no adverse event.

The content of the worst adverse event observed over the entire cycle in each case is shown above. Fourteen (30.4%) patients required at least one dose reduction of TAS‐102, primarily owing to anorexia. Twenty‐five (54.3%) patients required dose delays during the treatment period, predominantly owing to neutropenia. The median treatment interruption was 8 days (range, 1–28). No patient suffered from febrile neutropenia. Finally, no treatment‐related deaths were observed. Patients received the study treatment for a median of 6.5 cycles (range, 1–24 cycles). Discontinuation of protocol treatment was mainly due to disease progression (n = 39, 88.6%), and the remaining five cases were due to adverse events (11.4%). The median relative dose intensity of TAS‐102 and BEV was 80.9% (range, 44.0%–100%) and 81.5% (range, 50.0%–100%), respectively.