Table 3.
Immune regulatory SNPs and outcomes in patients receiving first-line FOLFIRI and cetuximab in FIRE-3 (validation cohort 1).
| SNP | Tumor Response | Progression-Free Survival | Overall Survival | ||||||
|---|---|---|---|---|---|---|---|---|---|
| N | PR | PD + SD | Median, ms (95% CI) |
Univariable HR (95% CI) |
Multivariable HR (95% CI) |
Median, ms (95% CI) |
Univariable HR (95% CI) |
Multivariable HR (95% CI) |
|
| IDO1 rs9657182 | |||||||||
| C/C | 63 | 39 (70%) | 17 (30%) | 9.6 (8.2, 13.0) | 1 (reference) | 1 (reference) | 28.7 (16.8, 38.3) | 1 (reference) | 1 (reference) |
| C/T | 86 | 48 (70%) | 21 (30%) | 9.7 (6.9, 11.3) | 1.18 (0.83, 1.69) | 1.09 (0.74, 1.61) | 25.2 (22.6, 33.6) | 1.15 (0.75, 1.76) | 0.90 (0.56, 1.43) |
| T/T | 72 | 49 (73%) | 18 (27%) | 10.0 (7.9, 11.5) | 1.06 (0.74, 1.54) | 1.13 (0.76, 1.68) | 36.6 (21.3, 52.0) | 0.84 (0.53, 1.32) | 0.73 (0.45, 1.17) |
| p-value * | 0.88 | 0.64 | 0.83 | 0.34 | 0.41 | ||||
| C/T or T/T | 158 | 97 (71%) | 39 (29%) | 10.0 (8.2, 10.9) | 1.12 (0.81, 1.55) | 1.11 (0.78, 1.57) | 28.0 (23.7, 37.5) | 0.99 (0.67, 1.45) | 0.81 (0.54, 1.22) |
| p-value * | 0.86 | 0.48 | 0.56 | 0.96 | 0.32 | ||||
| IDO1 rs3739319 | |||||||||
| G/G | 94 | 54 (69%) | 24 (31%) | 9.2 (7.9, 10.6) | 1 (reference) | 1 (reference) | 23.9 (20.6, 36.6) | 1 (reference) | 1 (reference) |
| G/A | 78 | 50 (69%) | 22 (31%) | 10.3 (7.8, 12.6) | 0.81 (0.59, 1.12) | 0.68 (0.48, 0.97) | 30.6 (22.6, 49.8) | 0.83 (0.56, 1.23) | 0.75 (0.49, 1.16) |
| A/A | 46 | 29 (74%) | 10 (26%) | 12.1 (8.7, 14.1) | 0.68 (0.46, 1.00) | 0.67 (0.45, 0.99) | 38.7 (27.9, 68.7) | 0.57 (0.35, 0.94) | 0.61 (0.36, 1.04) |
| p-value * | 0.88 | 0.12 | 0.040 | 0.079 | 0.14 | ||||
| G/A or A/A | 124 | 79 (71%) | 32 (29%) | 10.5 (8.8, 12.6) | 0.76 (0.57, 1.02) | 0.67 (0.50, 0.91) | 33.1 (27.6, 41.2) | 0.72 (0.50, 1.03) | 0.70 (0.48, 1.02) |
| p-value * | 0.87 | 0.059 | 0.011 | 0.068 | 0.063 | ||||
| CD24 rs52812045 | |||||||||
| G/G | 137 | 84 (72%) | 33 (28%) | 9.3 (7.9, 10.6) | 1 (reference) | 1 (reference) | 25.2 (20.6, 33.4) | 1 (reference) | 1 (reference) |
| G/A | 66 | 43 (68%) | 20 (32%) | 10.4 (8.0, 12.3) | 0.92 (0.67, 1.27) | 1.01 (0.72, 1.44) | 33.8 (24.5, 40.0) | 0.79 (0.53, 1.18) | 0.61 (0.38, 0.97) |
| A/A | 11 | 4 (57%) | 3 (43%) | 14.1 (5.7, 19.9) | 0.61 (0.32, 1.17) | 0.54 (0.26, 1.11) | 41.2 (19.9, 56.2) | 0.72 (0.33, 1.56) | 1.15 (0.50, 2.65) |
| p-value * | 0.56 | 0.31 | 0.24 | 0.40 | 0.093 | ||||
| G/A or A/A | 77 | 47 (67%) | 23 (33%) | 11.3 (9.0, 12.8) | 0.86 (0.64, 1.16) | 0.90 (0.65, 1.25) | 37.5 (26.5, 41.2) | 0.77 (0.53, 1.13) | 0.68 (0.44, 1.04) |
| p-value * | 0.51 | 0.32 | 0.55 | 0.18 | 0.074 | ||||
* p-value was based on Fisher’s exact test for tumor response, log-rank test for PFS and OS in the univariable analysis, and Wald test in the multivariable Cox proportional hazards regression model adjusting for sex, primary tumor site, liver metastases, number of metastatic sites, LDH, Kohne score, RAS and BRAF mutation status.