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

Powell, C.A.; Modi, S.; Iwata, H.; Takahashi, S.; Smit, E.F.; Siena, S.; ... ; Camidge, D.R. (2022)

Article / Letter to editor

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 benefit-risk 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.

• trastuzumab deruxtecan
• adverse event
• interstitial lung disease
• pneumonitis
• HER2

• All authors: Powell, C.A.; Modi, S.; Iwata, H.; Takahashi, S.; Smit, E.F.; Siena, S.; Chang, D.Y.; Macpherson, E.; Qin, A.; Singh, J.; Taitt, C.; Shire, N.; Camidge, D.R.
• Date: 2022-08-11
• Journal: ESMO Open
• Volume: 7
• Issue: 4
• DOI: doi:10.1016/j.esmoop.2022.100554
• Link: https://www.sciencedirect.com/science/article/pii/S205970292200182X?via%...