Background
Methods
NORDIC VII
FCGR2A-H131R and FCGR3A-V158F genotyping
Statistical analyses
Results
Patient characteristics
Actual frequency of genotypes (n) | Expected frequency of genotypes (n) | Hardy-Weinberg equilibrium X
2(1 degree of freedom) |
P-value | |
---|---|---|---|---|
FCGR2A
| ||||
H/H | 114 | 118.61 | 0.68 | 0.41 |
H/R | 261 | 251.78 | ||
R/R | 129 | 133.61 | ||
FCGR3A
| ||||
F/F | 241 | 238.10 | 0.37 | 0.54 |
F/V | 206 | 211.8 | ||
V/V | 50 | 47.10 |
FCGR2A
|
FCGR3A
| |||||||
---|---|---|---|---|---|---|---|---|
H/H
|
H/R
|
R/R
|
P-value |
F/F
|
F/V
|
V/V
|
P-value | |
Number of patients (%) | 114 (22.6%) | 261 (51.8%) | 129 (25.6%) | 241 (48.5%) | 206 (41.4%) | 50 (10.1%) | ||
Age, median (range) | 61 (27–74) | 62 (24–75) | 62 (30–75) | 0.99*
| 62 (24–75) | 61 (29–75) | 61 (35–75) | 0.47*
|
Sex, female/male | 49/65 | 102/159 | 57/72 | 0.58†
| 93/148 | 94/112 | 20/30 | 0.32†
|
Location, colon/rectum | 71/43 | 145/116 | 78/51 | 0.41†
| 147/94 | 121/85 | 23/27 | 0.15†
|
Metastatic sites, 1/>1 | 32/82 | 63/198 | 39/90 | 0.41†
| 62/179 | 51/155 | 20/30 | 0.08†
|
KRAS, wt/mutated | 62/38 | 150/82 | 61/49 | 0.26†
| 126/87 | 111/67 | 31/15 | 0.54†
|
BRAF, wt/mutated | 80/11 | 192/26 | 91/10 | 0.88†
| 182/18 | 141/21 | 36/7 | 0.28†
|
Treatment, FLOX/FLOX + cetuximab | 33/81 | 90/171 | 49/80 | 0.34†
| 79/162 | 75/131 | 15/35 | 0.58†
|
Response; response/no-response | 54/60 | 121/140 | 57/72 | 0.89†
| 109/132 | 93/113 | 25/25 | 0.82†
|
PFS (months), median | 8.3 | 7.9 | 7.6 | 0.45‡
| 7.9 | 7.6 | 8.4 | 0.76‡
|
OS (months), median | 21.9 | 19.8 | 18.2 | 0.42‡
| 19.9 | 20.5 | 19.7 | 0.77‡
|
Response rate and survival
Predictive analyses for benefit of cetuximab treatment
FLOX | FLOX + cetuximab | Interaction P-value | |||||
---|---|---|---|---|---|---|---|
FCGR2A
|
H/H
|
H/R
|
R/R
|
H/H
|
H/R
|
R/R
| |
Number of patients | N = 33 | N = 90 | N = 49 | N = 81 | N = 171 | N = 80 | |
Response (%) | 58% (19/33) | 41% (37/90) | 31% (15/49) | 43% (35/81) | 49% (84/171) | 53% (42/80) | 0.03*
|
PFS, median (months) | 8.4 | 7.9 | 7.5 | 8.3 | 7.8 | 7.6 | 0.35†
|
OS, median (months) | 28.0 | 20.5 | 19.8 | 21.4 | 19.5 | 17.3 | 0.85†
|
FCGR3A
|
F/F
|
F/V
|
V/V
|
F/F
|
F/V
|
V/V
| |
Number of patients | N = 79 | N = 75 | N = 15 | N = 162 | N = 131 | N = 35 | |
Response (%) | 38% (30/79) | 41% (31/75) | 53% (8/15) | 49% (79/162) | 47% (62/131) | 49% (17/35) | 0.63*
|
PFS, median (months) | 7.6 | 8.4 | 7.8 | 8.1 | 7.4 | 9.3 | 0.41†
|
OS, median (months) | 20.4 | 20.5 | 19.7 | 19.7 | 21.1 | 20.1 | 0.78†
|
FLOX | FLOX + cetuximab | ||||||
---|---|---|---|---|---|---|---|
H/H
|
H/R
|
R/R
|
H/H
|
H/R
|
R/R
| Interaction P-value | |
KRAS wild-type (N = 273) | |||||||
Number of patients | N = 16 | N = 52 | N = 20 | N = 46 | N = 98 | N = 41 | |
Response | 63% (10/16) | 42% (22/52) | 45% (9/20) | 46% (21/46) | 51% (50/98) | 56% (23/41) | 0.27*
|
PFS | 8.4 | 8.9 | 9.0 | 7.7 | 7.7 | 8.0 | 0.23†
|
OS | 31.6 | 23.6 | 19.0 | 21.4 | 20.7 | 18.9 | 0.23†
|
KRAS
mutated (N = 169)
| |||||||
Number of patients | N = 10 | N = 25 | N = 21 | N = 28 | N = 57 | N = 28 | |
Response | 60% (6/10) | 52% (13/25) | 19% (4/21) | 36% (10/28) | 46% (26/57) | 50% (14/28) | 0.04*
|
PFS | 8.1 | 8.3 | 7.1 | 7.7 | 8.1 | 6.7 | 0.90†
|
OS | 17.2 | 20.4 | 24.3 | 21.1 | 20.0 | 16.8 | 0.34†
|
BRAF
wild-type (N = 363)
| |||||||
Number of patients | N = 22 | N = 62 | N = 34 | N = 58 | N = 130 | N = 57 | |
Response | 64% (14/22) | 48% (30/62) | 35% (12/34) | 47% (27/58) | 52% (68/130) | 54% (31/57) | 0.10*
|
PFS | 9.3 | 8.9 | 7.7 | 8.5 | 8.1 | 8.0 | 0.47†
|
OS | 31.6 | 23.8 | 21.5 | 21.9 | 21.5 | 17.6 | 0.93†
|
BRAF
mutated (N = 47)
| |||||||
Number of patients | N =3 | N = 10 | N = 4 | N = 8 | N = 16 | N = 6 | |
Response | 33% (1/3) | 20% (2/10) | 0% (0/4) | 13% (1/8) | 25% (4/16) | 33% (2/6) | 0.72*
|
PFS | 4.3 | 5.1 | 3.8 | 3.8 | 4.6 | 5.8 | 0.36†
|
OS | 9.2 | 9.4 | 5.6 | 8.9 | 8.1 | 11.3 | 0.73†
|
FLOX | FLOX + cetuximab | ||||||
---|---|---|---|---|---|---|---|
F/F
|
F/V
|
V/V
|
F/F
|
F/V
|
V/V
| Interaction P-value | |
KRAS
wild-type (N =268)
| |||||||
Number of patients | N = 39 | N = 38 | N = 9 | N = 87 | N = 73 | N = 22 | |
Response | 44% (17/39) | 45% (17/38) | 56% (5/9) | 48% (42/87) | 51% (37/73) | 55% (12/22) | 0.95*
|
PFS | 7.8 | 9.0 | 8.4 | 8.0 | 7.3 | 11.8 | 0.72†
|
OS | 23.1 | 20.5 | 25.2 | 17.6 | 25.9 | 20.5 | 0.97†
|
KRAS
mutated (N =169)
| |||||||
Number of patients | N = 28 | N = 21 | N = 6 | N = 59 | N = 46 | N = 9 | |
Response | 36% (10/28) | 48% (10/21) | 50% (3/6) | 51% (30/59) | 39% (18/46) | 33% (3/9) | 0.28*
|
PFS | 7.8 | 8.1 | 4.0 | 8.3 | 7.0 | 6.9 | 0.19†
|
OS | 18.5 | 24.3 | 17.1 | 21.3 | 17.7 | 16.4 | 0.63†
|
BRAF
wild-type (N = 359)
| |||||||
Number of patients | N = 56 | N = 47 | N = 12 | N = 126 | N = 94 | N = 24 | |
Response | 45% (25/56) | 49% (23/47) | 50% (6/12) | 52% (65/126) | 48% (45/94) | 63% (15/24) | 0.71*
|
PFS | 7.9 | 9.1 | 7.8 | 8.3 | 7.6 | 11.5 | 0.58†
|
OS | 23.8 | 23.6 | 19.7 | 20.6 | 22.9 | 20.5 | 0.93†
|
BRAF
mutated (N = 46)
| |||||||
Number of patients | N = 8 | N = 7 | N = 2 | N = 10 | N = 14 | N = 5 | |
Response | 13% (1/8) | 14% (1/7) | 50% (1/2) | 20% (2/10) | 29% (4/14) | 0% (0/5) | 0.99*
|
PFS | 5.9 | 4.3 | 4.4 | 4.2 | 5.4 | 4.6 | 0.87†
|
OS | 9.5 | 9.4 | 5.2 | 10.8 | 8.9 | 10.3 | 0.66†
|