Table 3.
Time to treatment failure (TTF) for osimertinib (n = 154)
| Variable | N | Events | Median Months |
2-year survival % (95% CI) |
Cox univariate hazard ratio (95% CI) |
Cox univariate score p value |
Cox multivariate hazard Ratio (95% CI) |
Cox multivariate likelihood ratio p value (n = 154) |
|---|---|---|---|---|---|---|---|---|
| Age under 64 (median age) | 0.4976 | |||||||
| No | 77 | 41 (53%) | 13.8 | 36.2% (23.2%, 49.1%) | – | |||
| Yes | 77 | 43 (56%) | 18.2 | 41.9% (29.0%, 54.8%) | 0.86 (0.56, 1.32) | |||
| Gender | 0.0176 | 0.0327 | ||||||
| Female | 109 | 52 (48%) | 16.9 | 42.6% (31.1%, 54.2%) | – | – | ||
| Male | 45 | 32 (71%) | 10.2 | 30.4% (15.6%, 45.1%) | 1.70 (1.09, 2.64) | 1.72 (1.06, 2.80) | ||
| Race | 0.8212 | |||||||
| White | 126 | 70 (56%) | 14.1 | 39.5% (29.4%, 49.6%) | – | |||
| Non-white | 28 | 14 (50%) | 16.9 | 36.7% (14.2%, 59.1%) | 0.94 (0.53, 1.66) | |||
| Cigarette smoking status | 0.2781 | |||||||
| Never | 93 | 49 (53%) | 16.0 | 43.5% (31.6%, 55.4%) | – | |||
| Ever | 61 | 35 (57%) | 12.4 | 31.5% (17.1%, 45.8%) | 1.27 (0.82, 1.96) | |||
| Stage | 0.1484 | |||||||
| III | 9 | 2 (22%) | NR | 77.8% (50.6%, 100.0%) | 0.37 (0.09, 1.51) | |||
| IV | 145 | 82 (57%) | 14.1 | 36.9% (27.6%, 46.3%) | – | |||
| Cell type | 0.4601 | |||||||
| Adenocarcinoma | 150 | 82 (55%) | 14.6 | 39.1% (29.8%, 48.4%) | – | |||
| Non-adenocarcinoma | 4 | 2 (50%) | 19.7 | 0.0% (0.0%, 0.0%) | 0.59 (0.15, 2.42) | |||
| Surgery | 0.4342 | |||||||
| No | 140 | 79 (56%) | 14.1 | 37.8% (28.2%, 47.3%) | – | |||
| Yes | 14 | 5 (36%) | 52.2% (20.3%, 84.1%) | 0.70 (0.28, 1.73) | ||||
| Radiation | 0.8283 | |||||||
| No | 144 | 81 (56%) | 14.6 | 39.3% (30.0%, 48.7%) | – | |||
| Yes | 10 | 3 (30%) | 19.7 | 0.0% (0.0%, 0.0%) | 0.88 (0.28, 2.80) | |||
| T790M | 0.1236 | |||||||
| No | 59 | 29 (49%) | 11.8 | 21.2% (0.0%, 42.5%) | 1.44 (0.90, 2.30) | |||
| Yes | 95 | 55 (58%) | 16.6 | 43.7% (32.8%, 54.7%) | – | |||
| 1st EGFR mutation subtype | 0.5372 | |||||||
| Exon 19 deletion | 83 | 43 (52%) | 18.8 | 45.3% (32.6%, 58.1%) | – | |||
| Exon 21 L858R | 60 | 34 (57%) | 11.8 | 28.5% (13.9%, 43.0%) | 1.28 (0.82, 2.02) | |||
| Others | 11 | 7 (64%) | 11.7 | 40.0% (9.6%, 70.4%) | 1.23 (0.55, 2.74) | |||
| 1st TKI > 6 months | 0.5960 | |||||||
| No | 21 | 12 (57%) | 7.6 | 41.9% (20.4%, 63.4%) | 1.18 (0.64, 2.18) | |||
| Yes | 133 | 72 (54%) | 16.0 | 38.9% (28.9%, 49.0%) | – | |||
| 1st TKI > 12 months | < 0.0001 | 0.0019 | ||||||
| No | 65 | 45 (69%) | 6.8 | 19.0% (6.9%, 31.0%) | 2.60 (1.68, 4.02) | 2.16 (1.33, 3.50) | ||
| Yes | 89 | 39 (44%) | 24.4 | 53.7% (41.2%, 66.3%) | – | – | ||
| BMI drop > 10% | 0.0101 | 0.0207 | ||||||
| No | 118 | 57 (48%) | 17.9 | 43.5% (32.5%, 54.5%) | – | – | ||
| Yes | 36 | 27 (75%) | 8.2 | 24.5% (8.9%, 40.2%) | 1.81 (1.14, 2.86) | 1.85 (1.11, 3.08) | ||
| BMI increase > 10% | 0.3199 | |||||||
| No | 141 | 77 (55%) | 16.0 | 40.0% (30.5%, 49.6%) | – | |||
| Yes | 13 | 7 (54%) | 9.9 | 0.0% (0.0%, 0.0%) | 1.48 (0.68, 3.25) | |||
| Tumor in left lung | 0.9783 | |||||||
| No | 72 | 39 (54%) | 15.4 | 41.0% (27.3%, 54.7%) | 1.01 (0.65, 1.55) | |||
| Yes | 82 | 45 (55%) | 14.0 | 37.0% (24.5%, 49.5%) | – | |||
| Tumor in right lung | 0.6841 | |||||||
| No | 66 | 33 (50%) | 16.0 | 35.8% (20.8%, 50.7%) | 0.91 (0.59, 1.42) | |||
| Yes | 88 | 51 (58%) | 14.6 | 40.7% (28.9%, 52.5%) | – | |||
| Other cancer | 0.0755 | 0.4506 | ||||||
| No | 119 | 62 (52%) | 18.2 | 43.9% (33.3%, 54.5%) | – | – | ||
| Yes | 35 | 22 (63%) | 11.0 | 20.8% (3.4%, 38.3%) | 1.56 (0.95, 2.54) | 1.25 (0.70, 2.24) | ||
| Other pulmonary disease | 0.8054 | |||||||
| No | 134 | 72 (54%) | 14.6 | 38.2% (28.3%, 48.1%) | – | |||
| Yes | 20 | 12 (60%) | 17.9 | 41.9% (16.3%, 67.5%) | 0.93 (0.50, 1.71) | |||
| Any other disease | 0.3836 | |||||||
| No | 29 | 16 (55%) | 16.9 | 36.5% (15.9%, 57.0%) | 0.79 (0.46, 1.35) | |||
| Yes | 125 | 68 (54%) | 14.0 | 39.7% (29.4%, 49.9%) | – | |||
| ECOG performance status | 0.3443 | |||||||
| 0–1 | 138 | 75 (54%) | 16.0 | 40.2% (30.6%, 49.9%) | – | |||
| 2–4 | 16 | 9 (56%) | 9.9 | 0.0% (0.0%, 0.0%) | 1.40 (0.70, 2.82) | |||
| Lung metastasis | 0.1997 | |||||||
| No | 90 | 44 (49%) | 18.2 | 42.7% (30.2%, 55.3%) | – | |||
| Yes | 64 | 40 (63%) | 14.1 | 34.7% (21.4%, 48.0%) | 1.32 (0.86, 2.03) | |||
| Pleural metastasis | 0.8133 | |||||||
| No | 123 | 66 (54%) | 15.4 | 37.1% (26.7%, 47.6%) | – | |||
| Yes | 31 | 18 (58%) | 19.2 | 45.0% (25.0%, 65.0%) | 0.94 (0.56, 1.58) | |||
| CNS metastasis | 0.3727 | |||||||
| No | 130 | 67 (52%) | 16.1 | 40.2% (29.8%, 50.6%) | – | |||
| Yes | 24 | 17 (71%) | 12.5 | 32.7% (13.0%, 52.4%) | 1.27 (0.75, 2.17) | |||
| Bone metastasis | 0.0811 | 0.7694 | ||||||
| No | 78 | 38 (49%) | 19.2 | 48.7% (35.5%, 61.8%) | – | – | ||
| Yes | 76 | 46 (61%) | 10.9 | 29.1% (16.7%, 41.5%) | 1.46 (0.95, 2.25) | 1.08 (0.63, 1.85) | ||
| Liver metastasis | 0.0124 | 0.4444 | ||||||
| No | 138 | 72 (52%) | 16.6 | 41.7% (31.8%, 51.7%) | – | – | ||
| Yes | 16 | 12 (75%) | 6.6 | 16.0% (0.0%, 36.0%) | 2.16 (1.16, 4.00) | 1.34 (0.64, 2.84) | ||
| Peritoneum/abdomen LN metastasis | 0.7897 | |||||||
| No | 141 | 77 (55%) | 15.4 | 38.4% (28.7%, 48.1%) | – | |||
| Yes | 13 | 7 (54%) | 5.9 | 41.7% (13.8%, 69.6%) | 1.11 (0.51, 2.41) | |||
| Adrenal metastasis | 0.2315 | |||||||
| No | 142 | 77 (54%) | 16.1 | 40.1% (30.5%, 49.8%) | – | |||
| Yes | 12 | 7 (58%) | 9.8 | 22.2% (0.0%, 49.4%) | 1.60 (0.74, 3.48) | |||
| Distant metastasis number | 0.0578 | 0.4356 | ||||||
| Distant metastatic site = 0–1 | 88 | 43 (49%) | 18.2 | 41.6% (28.8%, 54.5%) | – | – | ||
| Distant metastatic site > 1 | 66 | 41 (62%) | 11.8 | 34.6% (21.5%, 47.7%) | 1.51 (0.98, 2.32) | 1.25 (0.71, 2.19) | ||
| PD-L1 expression | < 0.0001 | 0.0019 | ||||||
| < 50% | 61 | 34 (56%) | 11.8 | 29.3% (13.7%, 44.8%) | – | – | ||
| ≥ 50% | 10 | 8 (80%) | 3.3 | 0.0% (0.0%, 0.0%) | 3.12 (1.43, 6.81) | 4.28 (1.83, 10.02) | ||
| Not tested | 83 | 42 (51%) | 19.2 | 47.2% (34.9%, 59.5%) | 0.64 (0.41, 1.02) | 0.77 (0.48, 1.25) | ||
| Numbers of used EGFR-TKI before osimertinib | 0.5775 | |||||||
| 0–1 | 125 | 64 (51%) | 15.4 | 40.2% (29.8%, 50.7%) | – | |||
| 2–3 | 29 | 20 (69%) | 14.0 | 35.0% (16.2%, 53.7%) | 1.15 (0.70, 1.91) | |||
| 1st-line EGFR-TKI | < 0.0001 | 0.0136 | ||||||
| Erlotinib/Gefitinib | 126 | 64 (51%) | 18.2 | 44.2% (33.9%, 54.5%) | – | – | ||
| Afatinib | 28 | 20 (71%) | 6.3 | 0.0% (0.0%, 0.0%) | 3.16 (1.86, 5.40) | 2.19 (1.20, 3.98) | ||
| 1st-line EGFR-TKI | 0.1236 | |||||||
| Osimertinib as ≥ 2nd-line TKI without T790M | 59 | 29 (49%) | 11.8 | 21.2% (0.0%, 42.5%) | – | |||
| Osimertinib as ≥ 2nd-line TKI with T790M | 95 | 55 (58%) | 16.6 | 43.7% (32.8%, 54.7%) | 0.69 (0.43, 1.11) | |||
BMI body mass index, CI confidence interval, CNS central nervous system, ECOG Eastern Cooperative Oncology Group, EGFR epidermal growth factor receptor, LN lymph node, NR not reached, PD-L1 programmed cell death ligand 1, TKI tyrosine kinase inhibitor