1877P - Adverse effects (AEs) of trastuzumab deruxtecan (T-DXd) in solid tumours: A meta-analysis

Background

T-DXd is approved for use in several different solid tumours. Here we summarize its safety and tolerability profile.

Methods

Studies were identified from MEDLINE and proceedings of ASCO, ESMO and SABCS. Eligible studies were 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. Meta regression comprising linear regression weighted by sample size explored associations with AEs. Quantitative significance was defined as beta coefficient ≥ 0.28.

Results

Twenty-six studies comprising 3853 patients were included, with median age 57.5 years, 80% women & 57% of non-white ethnicity. In 12 studies patients were treated at both the 5.4 mg/kg and 6.4mg/kg dose. All grade (Mean, (95% CI)) AEs were seen in 98.9% & grade ≥3 AEs in 55.1%. Most common all grade AEs (≥25%) were nausea 69.2%, fatigue 37.2%, vomiting 36.2%, anemia 35.8%, alopecia 32.6%, diarrhea 28.6% & thrombocytopenia 26.4%. Most common (≥5%) grade ≥3 AEs were anemia 12.3%, thrombocytopenia 7%, fatigue 5.7% and nausea 5.4%. Interstitial lung disease (ILD) occurred in 13%, grade ≥3 ILD 2.1%, median time to ILD onset was 193 days (range 66.5-248), and 1% of patients died due to ILD. Treatment discontinuation without progression was observed in 17.1% of patients and deaths due to toxicity in 4.6%. Results of the meta regression are shown in the table. In bivariable analysis, associations between dose and grade ≥3 AEs and grade ≥3 ILD remained significant after adjustment for sex, ethnicity, region, and cancer site. Table: 1877P

Beta coefficients for meta-regression of associations with AEs