Transient Asymptomatic Pulmonary Opacities Occurring during Osimertinib Treatment

Abstract

Introduction Osimertinib is an Epidermal Growth Factor Receptor (EGFR) Inhibitor licensed for the treatment of EGFR mutant, T790M positive, non-small cell lung cancer (NSCLC). Previously unreported, common, transient asymptomatic pulmonary opacities (TAPOs) were noted at the University of Colorado in patients during osimertinib therapy. Methods CT imaging and clinical notes of NSCLC patients treated at the University of Colorado with osimertinib were retrospectively reviewed. Results Seven of twenty patients (35%), developed TAPOs while on osimertinib. The radiological patterns seen included ground-glass opacities with/without nodular consolidation. The median time to first lesion development was 8.7 weeks (range: 1.6 – 43 weeks) and 6 weeks (range: 1 – 11 weeks) to resolution during continued osimertinib. Conclusions TAPOs may be a previously unrecognized, benign feature associated with osimertinib therapy, which may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic, localized and there is no evidence of disease progression elsewhere it may be reasonable to continue treatment with osimertinib and monitor these lesions for resolution.

Osimertinib in patients with T790M mutation‐positive, advanced non–small cell lung cancer: Long‐term follow‐up from a pooled analysis of 2 phase 2 studies

“…Similarly, the safety profile of osimertinib was consistent between the pooled phase 2 trials and AURA3, with 4% of patients in both studies discontinuing osimertinib because of an AE deemed by the investigator as possibly causally related to treatment. 18 The radiologic patterns observed included ground-glass opacities with or without nodular consolidation. Furthermore, most of the new lesions that developed were extracranial, and only 8% of patients developed CNS lesions.…”

“…Noonan et al reported that 7 of 20 patients (35%) with NSCLC developed transient, asymptomatic pulmonary opacities while receiving osimertinib. 18 The radiologic patterns observed included ground-glass opacities with or without nodular consolidation. The lesion could be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis.…”

Transient Asymptomatic Pulmonary Opacities During Osimertinib Treatment and its Clinical Implication

“…Most patients who develop TAPOs are asymptomatic and radiological lesions are localized and disappear spontaneously without any intervention, which is consistent with previous reports. 14 Through comprehensive analysis of serial chest CT scans for patients who participated in three prospective clinical trials and treated with osimertinib, we were able to classify TAPO into three distinct radiological patterns such as COP, SEP, and nodular type. Among them, COP and SEP were most frequently observed.…”

“…13 Usually, these severe side effects may lead to permanent drug discontinuation. Recently, Noonan et al 14 reported novel interesting findings, so-called transient asymptomatic pulmonary opacities (TAPOs) that have not been reported previously. These opacities are asymptomatic, localized, and spontaneously disappeared in most of cases.…”

“…In some cases, TAPOs have recurred, either at the same or at different sites on the lung. Noonan et al 14 suggest that these lesions should be distinguished from pneumonia, disease progression, pulmonary edema, hemorrhage, radiation pneumonitis, and prior interstitial pneumonitis, which are differential diagnoses of ILD.…”