Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

Table 1 Patients characteristics n (%)

Characteristic	Folfiri 3 (n = 18)	Bevacizumab folfiri 3 (n = 99)	Aflibercept folfiri 3 (n = 36)	All (n = 153)	Comparison betweentreatments test P-value
Median age, yr (range)	62.5 (44-83)	64 (38-86)	66 (33-83)	64 (33-86)	0.33
Gender
Male	14 (67)	50 (51)	22 (61)	84 (55)	0.31
Female	6 (33)	49 (49)	14 (39)	69 (45)
Who performance status
0	2 (11)	12 (12)	6 (17)	20 (13)	0.47
1	11 (61)	75 (76)	25 (69)	111 (73)
2	5 (28)	12 (12)	5 (14)	22 (14)
Primary location
Right colon	3 (17)	33 (33)	8 (22)	44 (29)	0.51
Left colon	9 (50)	38 (39)	15 (42)	62 (41)
Rectum	6 (33)	28 (28)	13 (36)	47 (30)
Initial cancer status
Synchronous	14 (88)	26 (26)	20 (56)	46 (30)	0.09
Metachronous	4 (22)	73 (74)	16 (44)	107 (70)
Number of metastases
0 and 1	6 (33)	29 (29)	9 (25)	44 (29)	0.40
2	8 (40)	45 (46)	12 (33)	65 (42)
3 and more	4 (22)	25 (25)	15 (42)	44 (29)
Surgery of primary
No	7 (39)	38 (38)	14 (39)	59 (39)	1.00
Yes	11 (61)	61 (62)	22 (61)	94 (61)
Surgery of metastases
No	14 (78)	78 (79)	28 (88)	120 (81)	0.53
Yes	4 (22)	21 (21)	4 (12)	29 (19)
Unknown	-	-	4	4
Line of therapy
Second	5 (28)	17 (17)	4 (12)	26 (17)	0.52
Third	3 (17)	22 (22)	11 (31)	36 (24)
More	10 (55)	60 (61)	21 (57)	91 (59)
Irinotecan chemotherapy-naive
No	13 (72)	81 (82)	31 (86)	125 (82)	0.46
Yes	5 (28)	18 (18)	5 (14)	28 (18)
RAS/BRAF mutation status
Not mutated	11 (69)	36 (44)	16 (44)	63 (47)	0.18
At least one mutated	5 (31)	46 (56)	20 (56)	71 (53)
Unknown	2	17	-	19
Best overall response
PD	3 (17)	8 (8)	0 (0)	11 (7)	0.20
SD	1 (5)	9 (9)	7 (19)	17 (11)
PR	11 (61)	48 (48.5)	15 (42)	74 (48)
CR	0 (0)	3 (3)	1 (3)	4 (3)
NE	3 (17)	31 (31.5)	13 (36)	47 (31)
Median PFS, mo (95%CI)	3.0 (0.8-6.9)	3.7 (3.0-5.3)	4.7 (3.3-12.8)	3.9 (3.2-4.9)	-
Median OS, mo (95%CI)	5.6 (4.0-20.2)	8.5 (6.4-10.7)	13.7 (7.9-18.7)	9.4 (6.6-12.0)	-

PD: Progression disease; SD: Stable disease; PR: Partial response; CR: Complete response; NE: None evaluable; PFS: Progression free survival; OS: Overall survival.

Table 2 Summary of chemotherapy toxicity n (%)

Characteristic	Folfiri 3 (n = 18)	Bevacizumab folfiri 3 (n = 99)	Aflibercept folfiri 3 (n = 36)	All (n = 153)
Anemia
No	14	79	29	122
Grade 1	2	10	5	17
Grade 2	0	8	0	8
Grade 3	2	1	2	5
Grade 4	0	1	0	1
Thrombopenia
No	17	91	31	139
Grade 1	0	5	3	8
Grade 2	0	2	0	2
Grade 3	1	0	0	1
Grade 4	0	1	2	3
Neutropenia
No	13	87	26	126
Grade 1	1	0	1	2
Grade 2	2	1	4	7
Grade 3	1	9	4	14
Grade 4	1	2	1	4
Diarrheoa
No	9	48	11	68
Grade 1	2	18	8	28
Grade 2	5	14	5	24
Grade 3	2	14	11	27
Grade 4	0	5	1	6
Stomitis
No	13	83	27	123
Grade 1	2	5	5	12
Grade 2	2	8	4	14
Grade 3	0	1	0	1
Grade 4	1	2	0	3
Nausea
No	17	81	28	126
Grade 1	1	8	5	14
Grade 2	0	10	3	13
Vomiting
No	17	90	31	138
Grade 1	0	3	4	7
Grade 2	0	3	1	4
Grade 3	1	3	0	4
Hyperblood pressure
No	18	98	36	152
Yes	0	1	0	1
Bleeding
No	17	95	30	142
Yes	1	4	6	11
Venous thrombosis
No	18	97	36	151
Yes	0	2	0	2
Digestive perforation
No	18	98	36	152
Yes	0	1	0	1

Table 3 Results of Cox univariate analyses

Characteristic	Progression-free survival			Overall survival
	Hazard ratio	95%CI	P-value	Hazard ratio	95%CI	P-value
Age, yr
Continuous	0.999	0.984; 1.016	0.98	1.002	0.986; 1.018	0.81
Gender
Female	1			1
Male	0.827	0.597; 1.145	0.25	0.898	0.645; 1.251	0.53
Who performance status
0	1			1
1	1.569	0.926; 2.660	0.09	2.039	0.143; 3.639	0.02
2	2.827	0.473; 5.428	0.002	5.335	2.647; 10.75	< 0.01
Primary location
Right colon	1			1
Left colon	0.979	0.660; 1.454	0.92	0.945	0.634; 1.410	0.78
Rectum	1.018	0.671; 1.545	0.93	1.029	0.673; 1.572	0.90
Initial cancer status
Synchronous	1			1
Metachronous	0.815	0.572; 1.162	0.26	0.839	0.583; 1.208	0.34
No. of metastastatic sites
1	1			1
2	1.225	0.823; 1.823	0.32	1.241	0.824; 1.870	0.30
≥ 3	1.361	0.883; 2.098	0.16	1.490	0.954; 2.326	0.08
Surgery of primary
No	1			1
Yes	0.789	0.564; 1.104	0.17	0.799	0.568; 1.124	0.20
Surgery of metastases
No	1			1
Yes	0.592	0.388; 0.903	0.01	0.725	0.475; 1.107	0.13
Line of therapy
Second	1			1
Third	1.055	0.615; 1.812	0.85	1.126	0.646; 1.962	0.68
More	1.728	1.060; 2.816	0.03	1.531	0.931; 2.517	0.09
Treatment
FOLFIRI	1			1
FOLFIRI3 + Bevacizumab	1.055	0.615; 1.812	0.85	0.791	0.471; 1.329	0.38
FOLFIRI3 + Aflibercept	1.728	1.060; 2.816	0.03	0.470	0.255; 0.866	0.02
Irinotecan chemotherapy-naive
	1			1
No vs yes	0.731	0.474; 1.127	0.15	0.838	0.539; 1.303	0.43
RAS/BRAF mutation status
Not mutated	1			1
Mutated	0.910	0.641; 1.293	0.60	0.986	0.690; 1.408	0.94

Table 4 Results of Cox univariate analyses

Characteristic	Progression-free survival			Overall survival
	Hazard ratio	95%CI	P-value	Hazard ratio	95%CI	P-value
Age, yr
Continuous	0.990	0.968; 1.012	0.36	0.988	0.968; 1.007	0.22
Gender
Female	1			1
Male	1.003	0.673; 1.497	0.99	0.992	0.655; 1.502	0.97
Who performance status
0	1			1
1	1.588	0.832; 3.034	0.16	2.157	1.086; 4.284	0.03
2	2.165	0.925; 5.068	0.08	4.865	2.061; 11.49	< 0.001
Primary location
Right colon	1			1
Left colon	0.953	0.589; 1.541	0.84	0.919	0.556; 1.520	0.74
Rectum	1.054	0.634; 1.752	0.84	0.879	0.525; 1.470	0.62
Initial cancer status
Synchronous	1			1
Metachronous	0.862	0.554; 1.340	0.51	0.887	0.562; 1.398	0.60
Number of metastastatic sites
1	1			1
2	1.040	0.640; 1.692	0.87	1.085	0.654; 1.798	0.75
≥ 3	1.347	0.796; 2.279	0.27	1.449	0.847; 2.476	0.18
Surgery of primary
No	1			1
Yes	0.947	0.622; 1.442	0.80	0.893	0.575; 1.387	0.61
Surgery of metastases
No	1			1
Yes	0.562	0.342; 0.924	0.02	0.754	0.458; 1.241	0.27
Line of therapy
Second	1			1
Third	0.878	0.421; 1.832	0.73	0.944	0.441; 2.020	0.88
More	1.340	0.655; 2.740	0.42	1.155	0.548; 2.432	0.71
Treatment
FOLFIRI3	1			1
FOLFIRI3 + Bevacizumab	0.547	0.304; 0.983	0.04	0.647	0.354; 1.180	0.16
FOLFIRI3 + Aflibercept	0.354	0.181; 0.694	0.002	0.367	0.184; 0.729	0.004
Irinotecan chemotherapy-naive
No	1			1
Yes	0.979	0.548; 1.748	0.94	1.114	0.609; 2.038	0.73
RAS/BRAF mutation status
Not mutated	1			1
Mutated	1.045	0.679; 1.611	0.84	1.232	0.784; 1.935	0.37