Background: Trastuzumab deruxtecan (T-DXd) is a highly effective treatment for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer. Following two fatal pneumonitis cases within 6 months of introducing T-DXd, we implemented more intensive monitoring, including pre-treatment and daily home oxygen saturation measurements and 6-weekly chest imaging. We aimed to investigate the incidence of pneumonitis by grade after implementing this change. Materials and Methods: This paper presents a prospective single-institution observational study of all patients receiving at least one cycle of T-DXd at the Royal Marsden between 1 October 2021 and 30 September 2023, recording patients’ characteristics and treatments. Pneumonitis events were correlated with respiratory symptoms, oxygen saturations and chest imaging. Results: Fourteen patients (22%) developed pneumonitis after a median of eight cycles (range 1–20). Pneumonitis was detected in 2/14 upon emergency computed tomography (CT) scans, in 9/14 patients at the additional 6-weekly thorax CT and in 3/14 upon routine 12-weekly response-evaluation imaging. Pneumonitis was grade 1 in 6 patients, grade 2 in 7 patients and grade 5 in 1 patient. Amongst 8 symptomatic patients, 6/8 reported symptoms only when directly questioned. All 8 described either cough (6), dyspnoea (1) or wheeze (1) with or without fatigue (2). All pneumonitis patients had imaging responses (10) or stable disease (4) to T-DXd. Neither exertional oxygen saturations nor home oxygen saturation monitoring contributed to early pneumonitis diagnosis. Conclusions: Pneumonitis was more common in our real-world setting than in phase 3 trials. Despite intensive monitoring, only 6/14 patients with pneumonitis were diagnosed whilst asymptomatic. Careful patient counselling to report symptoms and their early investigation are critical adjuncts to regular CT scans to detect pneumonitis.
Walker et al. (Thu,) studied this question.