Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

Table 1 Baseline patient characteristics

Characteristic		Second-line, n = 22		Salvage therapy, n = 19		P value
Age, yr
	Median (range)	61.5	(29-73)	63	(42-81)	0.161
Sex
	Male	12	(55)	14	(74)	0.332
	Female	10	(45)	5	(26)
Tumor localization
	Left	14	(64)	13	(68)	1.002
	Right	8	(36)	6	(32)
Primary lesion resection
	Yes	12	(55)	15	(79)	0.192
	No	10	(45)	4	(21)
RAS status
	Wild	4	(18)	10	(53)	0.0262
	Mutant	18	(82)	9	(47)
RAF status
	Wild	1	(5)	0	(0)	1.002
	Unknown	21	(95)	19	(100)
Metastasis
	Liver	15	(68)	12	(63)	0.752
	Lung	7	(32)	8	(42)	0.532
	Others	14	(64)	11	(58)	0.702
Duration of prior AI administration
	< 6 mo	12	(55)	3	(16)	0.022
	≥ 6 mo	10	(45)	16	(84)
	Median, d (range)	144	(0-574)	323	(14-1119)	0.0061

Unless otherwise indicated, data are presented as n (%).

¹Student’s t-test.

²Fisher’s exact test.

AI: Angiogenesis inhibitor.

Table 2 Best response to treatment

Response		Second-line, n = 22		Salvage therapy, n = 19		P value
Best response
	Complete response	0		0
	Partial response	2		0
	Stable disease	8		7
	Progressive disease	9		7
	Unknown	3		5
Objective response rate		2	(11)	0	(0)	0.50
Disease control rate		10	(53)	7	(50)	1.00

Data are presented as n or n (%).

Table 3 Grade 3 or worse adverse events

Adverse event	Second-line, n = 22		Salvage therapy, n = 19
Leukopenia	0	(0)	2	(11)
Neutropenia	3	(14)	2	(11)
Febrile neutropenia	1	(5)	0	(0)
Vomiting	1	(5)	0	(0)
Diarrhea	0	(0)	1	(5)
Peripheral sensory neuropathy	0	(0)	2	(11)
Hypertension	2	(9)	1	(5)
Proteinuria	1	(5)	2	(11)
Perianal abscess	1	(5)	1	(5)

Data are presented as n (%).

Table 4 summary of data from recent reports including salvage therapy with three angiogenesis inhibitors plus chemotherapy

Treatment	Line	No. of patients	mTTP mo	MST mo	AE (grade ≥ 3)
FOLFIRI + Rmab[19]	3rd or later	13	4	6.1	NA
FOLFIRI + Rmab[20]	2nd	22	5.4	17.4	Neutropenia (54%)
					Hypertension (4%)
					Proteinuria (8%)
FOLFIRI + Rmab[20]	3rd or later	17	2.8	13	Neutropenia (35%)
					Hypertension (6%)
					Proteinuria (24%)
Cx + Bmab[21]	3rd or later	42	5.3	9.5	Neutropenia (43%)
					Hypertension (5%)
Cx + Bmab[22]	3rd or later	46	8.9	13.8	NA
Cx + Bmab[23]	2nd	154	8.5	19.1	Neutropenia (4%)
					Hypertension (1%)
Cx + Bmab[23]	3rd or later	62	6.3	14.9	Neutropenia (2%)
					Hypertension (2%)
					Proteinuria (2%)
FOLFIRI + AFL[18]	2nd	54	4.4	11.9	Neutropenia (9%)
					Hypertension (6%)
					Proteinuria (2%)
FOLFIRI + AFL[18]	3rd	69	4.3	11.1	Included in the above
FOLFIRI + AFL[18]	4th	47	3.4	8.1	Included in the above
FOLFIRI + AFL1	2nd	22	4.1	22.4	Neutropenia (14%)
					Hypertension (9%)
					Proteinuria (5%)
FOLFIRI + AFL1	3rd or later	19	2.4	13.2	Neutropenia (11%)
					Hypertension (5%)
					Proteinuria (11%)

¹They are our results.

mTTP: Median time to progression; MST: Median survival time; AE: Adverse event; Rmab: Ramucirumab; Cx: Chemotherapy (FOLFIRI or FOLFOX); Bmab: Bevacizumab; AFL: Aflibercept; FOLFIRI: Folinic acid-fluorouracil-irinotecan.