Transient Asymptomatic Pulmonary Opacities During Osimertinib Treatment and its Clinical Implication

• Published in: Journal of thoracic oncology 2018-08, Vol.13 (8), p.1106-1112
• Main Authors: Lee, Hansang, Lee, Ho Yun, Sun, Jong-Mu, Lee, Se-Hoon, Kim, Youjin, Park, Song Ee, Ahn, Jin Seok, Park, Keunchil, Ahn, Myung-Ju
• Format: Article
• Language: English
• Subjects: Acrylamides - adverse effects; Acrylamides - therapeutic use; Adult; Aged; Aged, 80 and over; Aniline Compounds - adverse effects; Aniline Compounds - therapeutic use; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Female; Humans; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Middle Aged; Multiple Pulmonary Nodules - chemically induced; Multiple Pulmonary Nodules - diagnostic imaging; Osimertinib; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Tomography, X-Ray Computed; Transient asymptomatic pulmonary opacities
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2018.04.038

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. 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. 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. 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.