Incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in breast cancer patients: A systematic review and single-arm meta-analysis

Abstract

Objective: We performed a systematic review and meta-analysis to assess the incidence and severity of those adverse
events (AEs) in metastatic breast cancer (mBC) patients treated with trastuzumab deruxtecan (T-DXd). Methodology: We
comprehensively searched PubMed, Cochrane, and Scopus databases for randomized clinical trials (RCTs) and observational cohort studies, including mBC patients with HER2-low or -positive expression who have received at least one dose
of T-DXd. The DESTINY-Breast02 study was also included after its presentation at the SABCS 2022. Our meta-analysis
followed the Cochrane Reviews and PRISMA statement guidelines. The statistical analysis was performed using the R
software, and the results are presented as pooled analysis in forest plots. Results: We included nine studies: three phase
III RCTs, three phase II and two phase I non-RCTs, and one retrospective cohort comprising 1,443 patients with a mean
follow-up of 14.9 months. The median age of our population ranged from 53 to 59 years. Most were non-Asian (40.5%)
and presented with hormone-receptor-positive mBC (66.8%). In a pooled analysis, the incidence of ILD was 13.0% (179
patients; 95%CI 11.0–13.0). Patients enrolled in phase III clinical trials had an ILD rate of 12.0%, while the observational
cohort reported a numerically higher rate of 18.0%. Most ILD cases, 84.9% (152 patients), were mild (grade 1 or 2). Grade 3
or 4 AEs were reported in 13 (7.3%) patients, and grade 5 in 14 (7.8%) patients. We assessed cardiotoxicity by the reduction
of left ventricular ejection fraction (LVEF) compared with baseline measures. Decreased LVEF was seen in 3.6% (95%CI
3.0–5.0%), and most patients were asymptomatic. A total of 11 patients developed prolonged QT interval, and four had
left ventricular dysfunction and cardiac failure. Conclusion: Our meta-analysis reinforces the importance of close vigilance for pulmonary and cardiac toxicities in mBC patients on treatment with T-DXd. Early detection and management
by a multidisciplinary team following the most recent guidelines may improve patient outcomes.