Abstract 1141P
Background
Osimertinib is associated with a relatively high frequency of interstitial lung disease (ILD). On the other hand, the occurrence of transient asymptomatic pulmonary opacities (TAPO) has been reported. In clinical setting, the frequency of TAPO and the pros and cons of osimertinib continuation is not clearly known.
Methods
This study was a multi-center, retrospective study. The purpose of this study is to research the frequency of ILD including TAPO and to evaluate the osimertinib continuation. We also evaluated progression-free survival (PFS), and performed subgroup analysis with each relevant factor, including TAPO.
Results
From August, 2018, to December, 2020, 133 patients were enrolled. The median age was 73.5 (range 40-90) years, males accounted for 36% (n:48), and females 64% (n:85). Smoking history was never 69%(n:92), past 27% (n:36), and current 4% (n:5) respectively. The median observation period was 632 days (8-1309 days). 28 patients (21.1%) experienced ILD events, 15 patients (11.3%) with CTCAE grade1, and 5 patients (3.8%) with grade2 and 8 patients (7%) with grade3 and above. Among the patients with grade1 ILD, 11 cases (8.3%) were considered to be TAPO, and all patients succeeded in continuation of osimertinib. The median time to the onset of TAPO after osimertinib administration was 27 weeks (range; 5.7-115.9). The median time to the disappearance of TAPO was 17 weeks (range; 8-36.4). The main finding of TAPO was a localized patchy shadow. The median PFS was 22 months (95% confidence interval:16.2-28.8 months). Patients with TAPO had a significant longer PFS than patients without TAPO. This result was confirmed in the multivariate analysis. Table: 1141P
Cox proportional-hazard models for time to progression-free survival
| Factor | Univariate | Multivariate | |||
| HR(95%CI） | p-value | HR(95%CI） | p-value | ||
| TAPO(vs no TAPO) | 0.12(0.02-0.84) | 0.03 | 0.12(0.02-0.89) | 0.04 | |
| ECOG-PS ≧2(vs PS 0-1) | 2.12(1.22-3.71) | 0.01 | 2.11(1.16-3.81) | 0.01 | |
| female sex(vs male sex) | 1.16(0.68-2.0) | 0.59 | 0.97(0.47-2.02) | 0.95 | |
| smoker(vs never smoker) | 0.91(0.53-1.55) | 0.72 | 0.94(0.47-1.88) | 0.85 | |
| EGFR mutation subtype | L858R | 1.04(0.63-1.71) | 0.89 | 0.83(0.49-1.42) | 0.51 |
| (vs exon19 del) | Uncommon | 0.99(0.3-3.26) | 0.99 | 0.7(0.21-2.36) | 0.56 |
Conclusions
This study showed that grade1 ILD might include TAPO and the patients with TAPO might be associated with good PFS. When the lung patchy shadows appear, it is important to consider the possibility of TAPO and to make an appropriate decision about osimertinib administration.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Motoko Tachihara.
Funding
Has not received any funding.
Disclosure
M. Tachihara: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd, Boehringer Ingelheim Japan Inc., Pfizer, Ono Pharmaceutical Co., Ltd, MSD K.K, Bristol Myers Squibb Co. Ltd., Novartis Pharmaceuticals K.K. Financial Interests, Institutional, Research Grant: AstraZeneca K.K. All other authors have declared no conflicts of interest.