Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

Abstract

Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

Recurrent Transient Asymptomatic Pulmonary Opacity with Long-Term Afatinib: A Case Report

“…Noonan et al [2] reported 7 TAPO cases out of 20 NSCLC subjects receiving osimertinib. Since then, some other studies reported TAPO with osimertinib and its incidence of 19.6–20.3% [3, 4]. But, considering the unresolved etiology of TAPO, it could occur in other EGFR-TKI.…”

“…TAPO might relate to long-term exposure to EGFR-TKI. On the other hand, Taronna et al [4] reported no difference of OS and time to treatment failure between TAPO positive and TAPO negative NSCLC receiving osimertinib. Further study is needed to reveal the clinical meaning of TAPO.…”

“…The efficacy of afatinib was reported in phase IIb study with median progression-free survival of 11.0 months and overall survival of 27.9 months [1]. Recently, TAPO was reported in EGFR-mutation harboring NSCLC receiving osimertinib [2][3][4]. However, TAPO related to other EGFR-TKI has not been reported.…”

“…Especially, lung injury is fatal in some cases and needs attention. Recently, transient asymptomatic pulmonary opacity (TAPO) was reported in EGFR-mutation harboring NSCLC receiving osimertinib [2][3][4]. However, TAPO related to other EGFR-TKI has not been reported.…”