Abstract 194P
Background
T-DXd is a highly effective treatment for HER2-positive and HER2-low advanced breast cancer (ABC). Following two cases of fatal pneumonitis at our institution within 6 months of introducing T-DxD in March 2021, we implemented more intensive monitoring with pre-treatment resting and exertional oxygen saturation measurement and 6-weekly chest imaging, with home oxygen saturation monitoring recommended.
Methods
A retrospective analysis of electronic medical records of all patients who received at least one cycle of T-DXd at the Royal Marsden 1st October 2021-30th September 2023. Patient characteristics, treatment and monitoring details were collected.
Results
Sixty-four patients, all female, received a median of 8 cycles of T-Dxd (range 1-34) at a median age of 57 years (range 30-80). Patients with HER2-positive ABC (53) had received a median of 2 prior lines of HER2-targeted therapy for ABC (range 0-5). Patients underwent a median of 5 chest CT scans (range 0-15). Pre-treatment exertional oxygen saturation monitoring was poorly documented, but neither pre-treatment exertional desaturation nor readings from home oxygen monitoring precipitated a diagnosis of pneumonitis. Fourteen patients (21.9%) developed pneumonitis after a median of 8 cycles (range 1-20). Pneumonitis was detected on emergency CT scan in 2, at the additional 6-weekly CT thorax in 9 patients and routine 12-weekly response-evaluation imaging in 3/14. Pneumonitis was grade 1 in 6, grade 2 in 7 and grade 5 in 1 patient. Amongst the 8 symptomatic patients, six reported symptoms only when questioned in clinic after planned chest imaging. All 8 reported either cough (6), dyspnoea (1) or wheeze (1) with or without fatigue (2). All patients with pneumonitis also had an imaging response (10) or stable disease (4) to T-DXd.
Conclusions
Pneumonitis was more common in our real-world setting than reported in phase III clinical trials. Despite 6-weekly chest imaging, pneumonitis was identified when asymptomatic in only 6/14 cases. Careful patient counselling to report symptoms and early investigation of respiratory symptoms are critical adjuncts to regular CT scans to detect pneumonitis.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Thwaites: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Conference attendance (BOPA): Novartis; Non-Financial Interests, Advisory Role: NICE. E. Kipps: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca; Financial Interests, Personal, Other, Consultancy: Novartis, Roche. M. Parton: Financial Interests, Personal, Invited Speaker: Pfizer, Gilead, Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, conference funding: MSD, Novartis; Financial Interests, Personal, Expert Testimony: Roche. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GSK, Repare therapeutics, GSK, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. A. Okines: Financial Interests, Institutional, Research Grant: Roche, Pfizer; Financial Interests, Personal, Invited Speaker: Seagen, Lily, Pfizer, AstraZeneca, Roche, Gilead, Eisai; Financial Interests, Personal, Advisory Board: Seagen, Pfizer, AstraZeneca, Roche; Financial Interests, Personal, Sponsor/Funding, Conference attendance: Novartis, Roche. All other authors have declared no conflicts of interest.