Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Clin Pharm Ther. 2022 Nov;47(11):1837-1844. doi: 10.1111/jcpt.13777. Epub 2022 Oct 6.
This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data.
We explored trastuzumab deruxtecan related adverse events (AEs) in clinical trials available in ClinicalTrials.gov and electronic databases (MEDLINE, EMBASE and PubMed) up to July 16, 2022. Meta-analysis was performed by using incidence rate with 95%CIs. In the pharmacovigilance study of FDA Adverse Event Reporting System (FAERS), the reporting odds ratio (ROR) and the medicines and healthcare products regulatory agency (MHRA) methods were used to analyse the real-world AEs (up to June 28, 2022).
A 8 clinical trials enrolled 1457 patients were included. The most common AEs of any grade were gastrointestinal disorders and blood and lymphatic system disorders. The most common AE of grade 3 or higher was neutropenia (21.4%, 95%CI: 14.7%-28.1%, I = 91%). The incidence of interstitial lung disease (ILD) and decreased left ventricular ejection fraction were 10.9% (95%CI: 7.2%-14.5%, I = 82%) and 1.2% (95%CI: 0.7%-2.2%, I = 98%), respectively. A total of 1244 AE reports were identified in the pharmacovigilance study. Gastrointestinal toxicity (ROR = 21.65), myelosuppression (ROR = 36.88), interstitial lung disease (ROR = 50.30), pneumonitis (ROR = 36.59), decreased ejection fraction (ROR = 16.08), and taste disorder (ROR = 14.06) mentioned in the instructions showed strong signals. Also, ascites (ROR = 14.90), lung opacity (ROR = 78.80), pulmonary fibrosis (ROR = 5.59), and increased KL-6 (ROR = 1761.97), which were not mentioned in the instructions, showed strong signals.
Trastuzumab deruxtecan was well tolerated, and more attention should be paid on ILD as well as decreased ejection fraction.
本研究旨在利用多源医学数据探讨曲妥珠单抗-deruxtecan（T-DXd，前身为 DS-8201a）的安全性概况。
我们在 ClinicalTrials.gov 和电子数据库（MEDLINE、EMBASE 和 PubMed）中检索截至 2022 年 7 月 16 日的临床试验中与曲妥珠单抗 deruxtecan 相关的不良事件（AE）。使用发生率和 95%CI 进行 Meta 分析。在 FDA 不良事件报告系统（FAERS）的药物警戒研究中，使用报告比值比（ROR）和药品和保健品管理局（MHRA）方法分析真实世界的 AE（截至 2022 年 6 月 28 日）。
共纳入 8 项临床试验，纳入 1457 例患者。任何等级最常见的 AE 是胃肠道疾病和血液及淋巴系统疾病。3 级或以上最常见的 AE 是中性粒细胞减少症（21.4%，95%CI：14.7%-28.1%，I²=91%）。间质性肺病（ILD）和左心室射血分数降低的发生率分别为 10.9%（95%CI：7.2%-14.5%，I²=82%）和 1.2%（95%CI：0.7%-2.2%，I²=98%）。药物警戒研究中共确定了 1244 例 AE 报告。胃肠道毒性（ROR=21.65）、骨髓抑制（ROR=36.88）、ILD（ROR=50.30）、肺炎（ROR=36.59）、射血分数降低（ROR=16.08）和味觉障碍（ROR=14.06）在说明书中提到具有强烈信号。此外，说明书中未提到的腹水（ROR=14.90）、肺不透明（ROR=78.80）、肺纤维化（ROR=5.59）和 KL-6 升高（ROR=1761.97）也具有强烈信号。
曲妥珠单抗 deruxtecan 具有良好的耐受性，ILD 和射血分数降低应引起更多关注。
