TABLE 6.
Association between SNPs and clinical outcomes (cont.).
| SNP-ID | Gene | Genotype | All grade ADRs [n/N (%)] | p-Value | Severity of ADRs [n/N (%)] | p-Value | TTF (months (95% CI)) | p-Value | PFS (months (95% CI)) | p-Value | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ADRs | Non-ADRs | Grade 1, 2 | Grade 3 | |||||||||
| rs762551 | CYP1A2 | C/C | 3/3 (100) | 0/3 (0) | 0.425 | 2/3 (66.7) | 1/3 (33.3) | 0.584 | NE | 0.987 | NE | 0.539 |
| C/A | 29/33 (87.9) | 4/33 (12.1) | 25/29 (86.2) | 4/29 (13.8) | 20.5 (15.2–25.7) | 30.0 (24.6–35.4) | ||||||
| A/A | 26/27 (96.3) | 1/27 (3.7) | 23/26 (88.5) | 3/26 (11.5) | 20.0 (2.2–37.8) | 42.0 (42.0–42.0) | ||||||
| CYP2A6*4 | CYP2A6 | non*4/non*4 | 49/54 (90.7) | 5/54 (9.3) | 0.450 | 42/49 (85.7) | 7/49 (14.3) | 0.639 | 21.2 (16.1–26.3) | 0.685 | 34.3 (16.9–52.7) | 0.847 |
| non*4/*4 | 9/9 (100) | 0/9 (0) | 8/9 (88.9) | 1/9 (11.1) | 15.7 (0.0–33.9) | 34.8 (28.5–40.1) | ||||||
| rs28399433 | CYP2A6 | A/A | 40/43 (93.0) | 3/43 (7.0) | 0.721 | 34/40 (85.0) | 6/40 (15.0) | 0.767 | 18.9 (13.1–26.7) | 0.181 | 33.3 (27.1–39.6) | <0.001* |
| A/C | 15/17 (88.2) | 2/17 (11.8) | 13/15 (86.7) | 2/15 (13.3) | 24.3 (15.1–33.6) | 42.0 (42.0–42.0) | ||||||
| C/C | 3/3 (100) | 0/3 (0) | 3/3 (100) | 0/3 (0) | 12.0 (0.0–27.7) | 6.0 (6.0–6.0) | ||||||
| rs1057910 | CYP2C9 | A/A | 53/57 (93.0) | 4/57 (7.0) | 0.563 | 48/53 (90.6) | 5/53 (9.4) | 0.003* | 23.0 (13.5–32.4) | 0.041* | 42.0 (42.0–42.0) | 0.010* |
| A/C | 4/5 (80.0) | 1/5 (20.0) | 2/4 (50.0) | 2/4 (50.0) | 14.0 (0.0–31.6) | 24.0 (9.3–38.7) | ||||||
| C/C | 1/1 (100) | 0/1 (0) | 0/1 (0) | 1/1 (100) | NE | NE | ||||||
| rs28371759 | CYP3A4 | A/A | 55/60 (91.7) | 5/60 (8.3) | 0.777 | 48/55 (87.3) | 7/55 (12.7) | 0.365 | 20.4 (15.4–25.4) | NE | 34.8 (29.8–39.9) | NE |
| A/G | 3/3 (100) | 0/0 (0) | 2/3 (66.7) | 1/3 (33.3) | NE | NE | ||||||
| rs776746 | CYP3A5 | A/A | 4/5 (80.0) | 1/5 (20.0) | 0.577 | 4/4 (100) | 0/4 (0) | 0.690 | 27.0 (23.1–30.9) | 0.835 | 30.0 (30.0–30.0) | 0.356 |
| A/G | 29/31 (93.5) | 2/31 (6.5) | 25/29 (86.2) | 4/29 (13.8) | 22.5 (14.3–30.7) | 37.7 (31.7–43.6) | ||||||
| G/G | 25/27 (92.6) | 2/27 (7.4) | 21/25 (84.0) | 4/25 (16.0) | 18.3 (11.1–25.4) | 28.6 (21.4–35.9) | ||||||
| rs1057868 | POR | C/C | 25/26 (96.2) | 1/26 (3.8) | 0.302 | 21/25 (84.0) | 4/25 (16.0) | 0.528 | 15.8 (6.4–25.2) | 0.259 | 30.0 (19.8–40.2) | 0.464 |
| C/T | 26/30 (86.7) | 4/30 (13.3) | 22/26 (84.6) | 4/26 (15.4) | 21.9 (16.1–27.7) | 42.0 (42.0–42.0) | ||||||
| T/T | 7/7 (100) | 0/7 (0) | 7/7 (100) | 0/7 (0) | NE | NE | ||||||
n, number of ADRs, in the genotype; N, number of all cases in the genotype; All grade ADRs, and Severity of ADRs (N = 63); TTF, median time to treatment failure (N = 20); PFS, median progression-free survival with osimertinib as second-line therapy (N = 36); 95% CI, 95% confidence interval; NE, not estimable.
a
Statistically significant.