Clinical and Imaging Features of Tepotinib‐Induced Interstitial Lung Disease in the Post‐Marketing Setting in Japan

The objective of this study was to investigate the clinical and imaging features of tepotinib-induced interstitial lung disease (ILD) using real-world data obtained during routine clinical use of tepotinib in Japan. The study was conducted as a voluntary safety-monitoring activity and targeted cases reported during the period from 1st June 2020 (the launch date of tepotinib in Japan) to 31st December 2023. An ILD adjudication committee, composed of external respiratory and radiology experts, assessed the clinical and imaging features of the ILD. The committee expertly identified 35 patients with tepotinib-induced ILD, with an estimated reported incidence of 2.9% (35/1190 patients). The estimated reported incidence of the fatal ILD was 0.9% (11/1190 patients). More than half of the ILDs were classified as ≤grade 2 (19/35 patients), with the predominant imaging pattern of organizing pneumonia (OP) (15/19 patients), followed by hypersensitivity pneumonitis (HP) and diffuse alveolar damage (DAD) patterns (3 and 1/19 patients, respectively). In contrast, among the ≥grade 3 ILDs (15/35 patients), DAD was the most frequently observed pattern (7/15 patients), followed by OP and HP patterns (6 and 2/15 patients, respectively). The median time to onset of the 35 ILDs from the start of tepotinib administration was 50.0 days (range: 4-205 days). Fatal outcomes occurred more frequently in patients with pre-existing ILD/interstitial lung abnormality (ILA) (8/12 patients), whereas most patients without pre-existing ILD/ILA experienced better outcomes of recovered/resolving (19/23 patients). These findings highlight the importance of close monitoring for ILD occurrence during the real-world clinical use of tepotinib.