TABLE 5.
Association between SNPs and clinical outcomes.
| 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 | |||||||||
| rs1128503 | ABCB1 | G/G | 9/9 (100) | 0/9 (0) | 0.150 | 7/9 (77.8) | 2/9 (22.2) | 0.682 | 34.0 (34.0–34.0) | 0.216 | 42.0 (42.0–42.0) | 0.283 |
| G/A | 28/29 (96.6)21/25 | 1/29 (3.4) | 25/28 (89.3) | 3/28 (10.7) | 21.9 (14.3–29.6) | 30.3 (24.7–35.8) | ||||||
| A/A | (84.0) | 4/25 (16.0) | 18/21 (85.7) | 3/21 (14.3) | 16.6 (11.1–22.1) | 30.9 (21.7–40.0) | ||||||
| rs2231142 | ABCG2 | C/C | 29/31 (93.5) | 2/31 (6.5) | 0.557 | 24/29 (82.8) | 5/29 (17.2) | 0.607 | 23.9 (17.4–30.3) | 0.420 | 39.0 (31.4–46.6) | 0.081 |
| C/A | 25/27 (92.6) | 2/27 (7.4) | 22/25 (88.0) | 3/25 (12.0) | 16.7 (9.0–24.4) | 26.7 (20.3–33.2) | ||||||
| A/A | 4/5 (80.0) | 1/5 (20.0) | 4/4 (100) | 0/4 (0) | 21.5 (0.0–46.0) | 42.0 (42.0–42.0) | ||||||
| rs2231164 | ABCG2 | T/T | 17/18 (94.4) | 1/18 (5.6) | 0.669 | 12/17 (70.6) | 5/17 (29.4) | 0.055 | 26.6 (18.3–34.9) | 0.128 | 37.5 (26.7–48.3) | 0.287 |
| T/C | 28/30 (93.3) | 2/30 (6.7) | 25/28 (89.3) | 3/28 (10.7) | 15.4 (9.2–21.6) | 30.0 (22.0–34.0) | ||||||
| C/C | 13/15 (86.7) | 2/15 (13.3) | 13/13 (100.0) | 0/13 (0) | 24.2 (12.8–35.6) | 39.0 (31.8–46.2) | ||||||
| rs2622604 | ABCG2 | C/C | 34/38 (89.5) | 4/38 (10.5) | 0.602 | 29/34 (85.3) | 5/34 (14.7) | 0.837 | 19.6 (13.3–26.0) | 0.825 | 30.0 (24.4–35.6) | 0.828 |
| C/T | 19/20 (95.0) | 1/20 (5.0) | 17/19 (89.5) | 2/19 (10.5) | 23.3 (10.6–35.9) | 42.0 (42.0–42.0) | ||||||
| T/T | 5/5 (100) | 0/5 (0) | 4/5 (80.0) | 1/5 (20.0) | 20.0 (14.1–25.9) | NE | ||||||
| rs4148157 | ABCG2 | G/G | 36/38 (94.7) | 2/38 (5.3) | 0.447 | 29/36 (80.6) | 7/36 (19.4) | 0.271 | 20.9 (15.4–25.4) | 0.930 | 35.7 (28.3–43.0) | 0.529 |
| G/A | 19/22 (86.4) | 3/22 (13.6) | 18/19 (94.7) | 1/19 (5.3) | 19.0 (8.3–29.7) | 30.5 (25.2–35.9) | ||||||
| A/A | 3/3 (100) | 0/3 (0) | 3/3 (100) | 0/3 (0) | 21.5 (0.0–46.0) | 42.0 (42.0–42.0) | ||||||
| rs1871744 | ABCG2 | T/T | 24/27 (88.9) | 3/27 (11.1) | 0.459 | 20/24 (83.3) | 4/24 (16.7) | 0.806 | 16.8 (9.2–24.4) | 0.734 | 35.7 (28.6–42.8) | 0.540 |
| T/C | 28/29 (96.6) | 1/29 (3.4) | 25/28 (89.3) | 3/28 (10.7) | 23.3 (15.9–30.6) | 29.1 (23.3–34.9) | ||||||
| C/C | 6/7 (85.7) | 1/7 (14.3) | 5/6 (83.3) | 1/6 (16.7) | 27.0 (19.2–34.8) | 42.0 (42.0–42.0) | ||||||
| rs2069514 | CYP1A2 | G/G | 28/31 (90.3) | 3/31 (9.7) | 0.752 | 23/28 (82.1) | 5/28 (17.9) | 0.534 | 24.0 (18.6–29.4) | <0.001 a | 38.4 (33.1–43.7) | 0.166 |
| G/A | 25/27 (92.6) | 2/27 (7.4) | 22/25 (88.0) | 3/25 (12.0) | 16.0 (11.8–20.2) | 26.3 (21.4–31.2) | ||||||
| A/A | 5/5 (100) | 0/5 (0) | 5/5 (100) | 0/5 (0) | 3.0 (3.0–3.0) | 22.0 (9.1–34.8) | ||||||
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.