Table 3.
Characteristics at EGFR-TKI re-administration
| Characteristic | Total (n = 58) | TKI re-administration-induced ILD ( +) (n = 13) | TKI re-administration-induced ILD ( −) (n = 45) | P value |
|---|---|---|---|---|
| Age*, average (range) | 71 (39–85) | 69 (57–84) | 71 (39–85) | 0.96 |
| Gender, male/female | 25/33 | 9/4 | 16/29 | 0.05 |
| Smoking history, smoker/never smoker | 29/29 | 8/5 | 21/24 | 0.53 |
| Pack-years in smokers, average (range) | 27 (1–144) | 33.5 (0.5–54) | 27 (1.25–144) | 0.53 |
| ECOG performance status, 0/1/2 | 12/39/7 | 1/10/2 | 11/29/5 | 0.42 |
| Type of EGFR mutation, exon19del/L858R/exon19del + T790M/unknown | 27/28/1/2 | 5/7/0/1 | 22/21/1/1 | 0.75 |
| EGFR T790M, yes/no | 6/52 | 3/10 | 3/42 | 0.12 |
| Clinical stage, III/IV/relapse | 6/35/17 | 1/5/7 | 5/30/10 | 0.09 |
| Status of TKI re-administration | ||||
| TKI used at re-administration | ||||
| Gefitinib | 14 | 4 | 10 | 0.88 |
| Erlotiniba,b | 15 | 3# | 12$ | |
| Afatinib | 13 | 2 | 11 | |
| Dacomitinib | 1 | 0 | 1 | |
| Osimertinib | 15 | 4 | 11 | |
| Same/Different from initial TKI | 17/41 | 6/7 | 11/34 | 0.17 |
| Individual TKI administration pattern | ||||
| Gefitinib as first time use | 12 | 1 (8%) | 11 | < 0.01 |
| Gefitinib as 2nd time use | 3 | 3 (100%) | 0 | |
| Erlotinib as first time use | 12 | 1 (8%) | 11 | |
| Erlotinib as 2nd time use | 3 | 2 (67%) | 1 | |
| Afatinib as first time use | 12 | 2 (17%) | 10 | |
| Dacomitinib as first time use | 1 | 0 (0%) | 1 | |
| Osimertinib as first time use | 4 | 3 (75%) | 1 | |
| Osimertinib as 2nd time use | 11 | 1 (9%) | 10 | |
| Therapeutic line, 2/3/4/5/6/7th | 17/18/12/7/0/4 | 5/5/2/1/0/0 | 12/13/10/6/0/4 | 0.66 |
| Treatment with corticosteroid, dosage of prednisolone at the start of TKI re-administration (mg) | ||||
| Yes / no | 17 / 41 | 4 / 9 | 13 / 32 | 1.00 |
| 0/2.5/5/10/15/20/over 25 | 41/3/3/3/3/2/3 | 9/0/2/0/1/1/0 | 32/3/1/3/2/1/3 | |
| Response | ||||
| PR/SD/PD/NE | 28/20/3/7 | 5/5/1/2 | 23/15/2/5 | 0.74 |
| Response rate (%)/Disease control rate (%) | 55/94 | 45/91 | 58/95 | 0.51 |
| Status of initial TKI-induced ILD | ||||
| CTCAE Grade, 1/2/3/4 | 26/20/11/1 | 5/6/2/0 | 21/14/9/1 | 0.75 |
| Onset, days from initial TKI, median (range) | 61 (4–537) | 51 (15–537) | 61 (4–457) | 0.42 |
| Radiological pattern of initial TKI-induced ILD, DAD/non-DAD/undetermined | 4/53/1 | 0/13/0 | 4/40/1 | 0.56 |
| Dosage of corticosteroid (prednisolone, mg), median (range) | 45 (10–70) | 40 (20–60) | 50 (10–70) | 0.45 |
| Duration of corticosteroid, median (range), days, median (range) | 56 (7–511) | 52 (24–112) | 70 (7–511) | 0.07 |
| Duration between stopping of corticosteroid and TKI re-administration, days, mean (range) | 96 (0–853) | 66 (0–461) | 99 (0–853) | 0.67 |
| Duration between onset of initial TKI-induced ILD and TKI re-administration, days, median | 119 (7–892) | 76 (20–594) | 128 (7–892) | 0.70 |
| Radiological finding at TKI re-administration, remained/disappeared | 27/31 | 8/5 | 19/26 | 0.22 |
CTCAE common terminology criteria for adverse events, CR complete response, DAD diffuse alveolar damage, ECOG Eastern Cooperative Oncology Group, ILD interstitial lung disease, NE not evaluated, PD progressive disease, PR partial response, SD stable disease, TKI tyrosine kinase inhibitor
*At diagnosis for lung cancer
aOne patient was treated with addition of bevacizumab
bTwo patients were treated with addition of ramucirumab