Monitoring for pneumonitis in breast cancer patients treated with trastuzumab deruxtecan: a single-centre experience

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.