Enhertu and interstitial lung disease
 

Pooled analysis of drug-related interstitial lung disease and/or pneumonitis
in nine trastuzumab deruxtecan monotherapy studies

https://www.esmoopen.com/action/show...2822%2900182-X

Introduction: This pooled analysis of nine phase I and II trastuzumab deruxtecan (T-DXd) monotherapy studies
described drug-related interstitial lung disease (ILD)/pneumonitis in patients treated with T-DXd.

Methods: Patients who received T-DXd across nine studies were included. Investigator-assessed ILD/pneumonitis events
were retrospectively reviewed by an independent adjudication committee; events adjudicated as drug-related ILD/
pneumonitis are summarized.

Results: The analysis included 1150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal
cancer, 9.3%; other cancer, 3.0%). Median treatment duration was 5.8 (range, 0.7-56.3) months, with a median of 4
(range, 1-27) prior lines of therapy. The overall incidence of adjudicated drug-related ILD/pneumonitis was 15.4%
(grade 5, 2.2%). Most patients with ILD/pneumonitis experienced low-grade events (grade 1 or 2, 77.4%); 87.0%
had their first event within 12 months [median, 5.4 (range, <0.1-46.8) months] of their first dose of T-DXd. Based
on data review, adjudicated ILD/pneumonitis onset occurred earlier than identified by investigators for 53.2% of
events [median difference in onset date, 43 (range, 1-499) days]. Stepwise Cox regression identified several baseline
factors potentially associated with increased risk of adjudicated drug-related ILD/pneumonitis: age <65 years,
enrollment in Japan, T-DXd dose >6.4 mg/kg, oxygen saturation <95%, moderate/severe renal impairment,
presence of lung comorbidities, and time since initial diagnosis >4 years.

Conclusions: In this pooled analysis of heavily treated patients, the incidence of ILD/pneumonitis was 15.4%, with most
being low grade and occurring in the first 12 months of treatment. The benefiterisk of T-DXd treatment is positive;
however, some patients may be at increased risk of developing ILD/pneumonitis, and further investigation is needed
to confirm ILD/pneumonitis risk factors. Close monitoring and proactive management of ILD/pneumonitis are
warranted for all.