Adverse effect of trastuzumab deruxtecan in solid tumours: A systematic review and meta-analysis

Introduction

Trastuzumab deruxtecan (T-DXd) is approved for use in numerous solid tumours. Here we summarize its safety and tolerability profile.

Methods

Studies were identified from MEDLINE, EMBASE and recent conference proceedings. Analysis comprised clinical trials (phases 1 [dose-expansion], 2 or 3) reporting safety and tolerability of T-DXd. Data were pooled as the mean weighted by individual study sample size from single arm studies. Randomized studies were analyzed separately to compare T-DXd to chemotherapy and to trastuzumab emtansine. Meta regression comprised linear regression weighted by sample size was performed.

Results

A total of 35 studies with 48 distinct cohorts were included in the analysis. All grade adverse effects (AEs) and grade ≥ 3 AEs occurred in 97.2 % and 54.9 % of patients respectively. Most common all grade AEs included: nausea (66.2 %), fatigue (41.8 %) and anemia (33.8 %). Common grade ≥ 3 AEs included anemia (12.9 %), thrombocytopenia (6.7 %) and fatigue (5.3 %). Pooled incidence rate of interstitial lung disease (ILD) and grade≥ 3 ILD were 13.2 % and 2.3 % respectively, and 2 % had febrile neutropenia. Cardiotoxicity was rare. Treatment- and ILD- related deaths were reported in 5 % and ILD 1.4 %, respectively. Compared to chemotherapy, T-DXd had higher odds of AEs and treatment discontinuation. Higher dose, non-Caucasian ethnicity and cancer sites other than breast were associated with grade ≥ 3 AE, grade ≥ 3 ILD, AE- and ILD- related deaths and serious AEs.

Conclusions

T-DXd has a safety and tolerability profile less favorable than classical chemotherapy. Dose, ethnicity and cancer site are associated with differential safety and tolerability.