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Transient Asymptomatic Pulmonary Opacities During Osimertinib Treatment and its Clinical Implication
Hansang Lee1, Ho Yun Lee2, Jong-Mu Sun1
1Division of Hematology-Oncology, Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Introduction:
Osimertinib is an oral, potent, irreversible third-generation EGFR tyrosine kinase inhibitor approved for the treatment of T790M-positive NSCLC patients who failed first- or second-generation EGFR tyrosine kinase inhibitors. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1% to 3% of patients. Recently, a relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs), which are different from ILD, has been described. However, its clinical implication has not been fully determined yet.
Methods:
We retrospectively analyzed 74 EGFR T790M mutant NSCLC patients treated with osimertinib. Serial computed tomographic findings were reviewed by a thoracic radiologist independently, and TAPO was classified according to its radiologic pattern. We also analyzed the correlation of TAPO with clinical outcomes.
Results:
Among 74 patients, TAPOs were found in 15 (20.3%). The median time to TAPO development was 24.0 weeks (range, 1 to 72 weeks) and the median duration of TAPO was 6.0 weeks (range, 5 to 24 weeks) during continued osimertinib treatment. The most common radiological patterns of TAPO include cryptogenic organizing pneumonia and/or simple eosinophilic pneumonia. There was no significant difference in patient characteristics between TAPO-positive and -negative groups. The duration of exposure to osimertinib was significantly longer in TAPO-positive than -negative groups (25.0 months versus 13.0 months, p = 0.009). The median progression-free survival and the median overall survival was numerically longer in TAPO-positive than -negative groups (22 months versus 15 months for progression-free survival, p = 0.293; 37 months versus 24 months for overall survival, p = 0.059), respectively.
Conclusions:
TAPOs are frequently observed with osimertinib treatment and may be mistaken for isolated pulmonary progression or drug-induced ILD. Given the lack of serious clinical deterioration, it is reasonable to continue osimertinib with regular computed tomographic-scan follow-up. For further clinical validation of TAPOs, long-term follow-up and large studies are warranted.
Insights
Transient asymptomatic pulmonary opacities (TAPOs) are common in patients treated with osimertinib for non-small cell lung cancer. Continued treatment with regular monitoring is often feasible, as TAPOs do not typically cause serious clinical issues.
Area of Science:
- Pulmonology
- Oncology
- Radiology
Background:
- Osimertinib is a third-generation EGFR inhibitor for T790M-positive NSCLC.
- Interstitial lung disease (ILD) is a rare complication of osimertinib.
- Transient asymptomatic pulmonary opacities (TAPOs) are increasingly recognized but their clinical significance is unclear.
Purpose of the Study:
- To investigate the incidence, characteristics, and clinical outcomes of TAPOs in patients receiving osimertinib.
- To differentiate TAPOs from ILD and pulmonary progression.
Main Methods:
- Retrospective analysis of 74 EGFR T790M mutant NSCLC patients treated with osimertinib.
- Review of serial CT findings by a thoracic radiologist.
- Classification of TAPO patterns and analysis of correlation with clinical outcomes.
Main Results:
- TAPOs were observed in 20.3% of patients.
- The median time to TAPO development was 24 weeks, with a median duration of 6 weeks.
- TAPO-positive patients had longer osimertinib exposure and numerically longer progression-free and overall survival.
Conclusions:
- TAPOs are frequently observed during osimertinib treatment and can be mistaken for ILD or progression.
- Continued osimertinib treatment with regular CT monitoring is reasonable due to lack of serious deterioration.
- Further large-scale studies are needed for clinical validation of TAPOs.
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