Pathak Neha, Di Iorio Massimo, Gimenez Diego Malon, Berner-Wygoda Yael, Savill Jacqueline, Aljuhani Amal, Mittal Abhenil, Kumar Vikaash, Amir Eitan
Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
Department of Oncology, Lakeshore General Hospital, Montreal, QC, Canada.
Crit Rev Oncol Hematol. 2025 Sep;213:104787. doi: 10.1016/j.critrevonc.2025.104787. Epub 2025 Jun 2.
Trastuzumab deruxtecan (T-DXd) is approved for use in numerous solid tumours. Here we summarize its safety and tolerability profile.
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.
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.
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.
曲妥珠单抗德曲妥珠单抗（T-DXd）已被批准用于多种实体瘤。在此，我们总结其安全性和耐受性概况。
从MEDLINE、EMBASE和近期会议论文集中检索研究。分析包括报告T-DXd安全性和耐受性的临床试验（1期[剂量扩展]、2期或3期）。数据汇总为单臂研究中按个体研究样本量加权的均值。对随机研究进行单独分析，以比较T-DXd与化疗以及曲妥珠单抗恩美曲妥珠单抗。进行样本量加权的线性回归的Meta回归。
分析共纳入35项研究，包含48个不同队列。所有级别不良反应（AE）和≥3级AE分别发生在97.2%和54.9%的患者中。最常见的所有级别AE包括：恶心（66.2%）、疲劳（41.8%）和贫血（33.8%）。常见的≥3级AE包括贫血（12.9%）、血小板减少（6.7%）和疲劳（5.3%）。间质性肺病（ILD）和≥3级ILD的汇总发生率分别为13.2%和2.3%，2%的患者发生发热性中性粒细胞减少。心脏毒性罕见。分别有5%的患者报告了与治疗相关的死亡和1.4%的患者报告了与ILD相关的死亡。与化疗相比，T-DXd发生AE和治疗中断的几率更高。更高剂量、非白种人种族以及非乳腺癌部位与≥3级AE、≥3级ILD、与AE和ILD相关的死亡以及严重AE相关。
T-DXd的安全性和耐受性概况不如传统化疗。剂量、种族和癌症部位与不同的安全性和耐受性相关。
