Smith Judith A, Medina Patrick, Miao Mary, Moore Kathleen N
Department of Obstetrics, Gynecology, and Reproductive Sciences, UTHealth Houston McGovern Medical School, Houston, TX.
Department of Pharmacy, UTHealth Houston Memorial Hermann Cancer Center, Texas Medical Center, Houston, TX, USA.
Am J Health Syst Pharm. 2025 May 21;82(10):522-536. doi: 10.1093/ajhp/zxaf011.
To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).
A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces receptor-mediated internalization, lysosomal degradation, and release of DM4-containing cytotoxic metabolites. Meaningful anticancer activity in PROC was demonstrated in the single-arm phase 2 SORAYA trial (objective response rate, 32.4%; 95% confidence interval, 23.6%-42.2%) and the confirmatory, randomized phase 3 MIRASOL trial (median progression-free survival with mirvetuximab soravtansine-gynx vs chemotherapy, 5.62 vs 3.98 months; hazard ratio, 0.65; 95% confidence interval, 0.52-0.81; P < 0.0001]). Ocular disorders (eg, keratopathy and blurred vision), nausea, diarrhea, and fatigue were among the most common adverse events (AEs) that occurred during clinical trials.
This review of trial data and pharmacology information for AIBW dosing of mirvetuximab soravtansine-gynx will help support its integration into the PROC treatment landscape. The review also discusses recommendations for prophylaxis, monitoring, and management of common AEs, including eye drop regimens, to mitigate ocular events. Mirvetuximab soravtansine-gynx is an effective, novel agent for PROC that targets a newly established biomarker. Established interventions can help mitigate AEs and support the safe use of mirvetuximab soravtansine-gynx.
评估mirvetuximab soravtansine-gynx的药理学、疗效、安全性以及给药和用药注意事项（包括基于调整后的理想体重[AIBW]给药），这是一种用于铂耐药卵巢癌（PROC）的首创叶酸受体α（FRα）导向抗体药物偶联物。
在PubMed中使用“卵巢癌”和“mirvetuximab soravtansine”检索从创刊至2024年4月16日发表的文章。对相关出版物、摘要和临床试验进行了综述。Mirvetuximab soravtansine-gynx的给药剂量为每3周6 mg/kg AIBW，它由一种结合FRα的抗体、一个亲水性二硫键连接子和一个美登素类DM4有效载荷组成。Mirvetuximab soravtansine-gynx与FRα结合，诱导受体介导的内化、溶酶体降解以及含DM4的细胞毒性代谢产物的释放。在单臂2期SORAYA试验（客观缓解率为32.4%；95%置信区间为23.6%-42.2%）和确证性随机3期MIRASOL试验（使用mirvetuximab soravtansine-gynx与化疗相比的中位无进展生存期分别为5.62个月和3.98个月；风险比为0.65；95%置信区间为0.52-0.81；P<0.0001）中均显示出在PROC中有显著的抗癌活性。眼部疾病（如角膜病变和视力模糊）、恶心、腹泻和疲劳是临床试验期间最常见的不良事件（AE）。
对mirvetuximab soravtansine-gynx基于AIBW给药的试验数据和药理学信息进行的这项综述，将有助于支持其融入PROC的治疗格局。该综述还讨论了针对常见AE的预防、监测和管理的建议，包括眼药水方案，以减轻眼部事件。Mirvetuximab soravtansine-gynx是一种针对新确立的生物标志物的有效、新型的PROC治疗药物。既定的干预措施有助于减轻AE并支持mirvetuximab soravtansine-gynx的安全使用。
