Clinical and imaging features of interstitial lung disease in cancer patients treated with trastuzumab deruxtecan

Abstract

Background Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. Methods Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. Results The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25–143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. Conclusions This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome.

Trastuzumab deruxtecan versus treatment of physician’s choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study

“…These findings are similar to previous reports of higher risk of ILD or pneumonitis with T-DXd treatment in Japanese patients [24], and may be linked to underlying biologic factors or Japanese-specific management/monitoring practices. Further, a real-world study of T-DXd use in Japan since its launch in 2020 reported that the most common ILD radiologic patterns were organizing pneumonia, hypersensitivity pneumonitis, and diffuse alveolar damage (DAD), with the DAD subtype being associated with poor prognosis [25]. Based on experience of gefitinibinduced ILD [26], healthcare providers in Japan have a high awareness of ILD and more experience in proactively detecting ILD, even at grade 1 stage (i.e., ILD manifesting only as abnormal high-resolution computed tomography) and intensively managing ILD.…”