Johannet Paul, Flint Matthew, Chui M Herman, Konner Jason, Friedman Claire, Green Angela K, Guo Robin, Hensley Martee L, Kyi Chrisann, Liu Ying, Makker Vicky, Rubinstein Maria, Sabbatini Paul, Tew William P, Foote Michael B, Weigelt Britta, Aghajanian Carol, Grisham Rachel N, O'Cearbhaill Roisin E
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gynecol Oncol. 2025 Apr;195:173-179. doi: 10.1016/j.ygyno.2025.03.023. Epub 2025 Mar 22.
Mirvetuximab soravtansine-gynx (MIRV) is a FOLR1-binding antibody-drug conjugate (ADC) with a microtubule inhibitor payload. We investigated MIRV's efficacy, toxicity profile, and determinants of resistance in a cohort of patients with recurrent/persistent high FOLR1-expressing high-grade serous ovarian cancer (HGSOC).
This retrospective study included 170 patients with recurrent/persistent FOLR1-high (≥75 % of tumor cells with ≥2+ membranous staining intensity) HGSOC who received standard-of-care MIRV monotherapy. We evaluated progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method and multivariable Cox proportional hazards models. We classified adverse events using CTCAE v5.0.
Overall, median PFS was 3.5 months (95 % CI, 3.0-4.1). However, 22.4 % had PFS ≥6 months and were less likely to have progressed on or within one month of prior taxane-based therapy (P = 0.008). Patients with previous progression on a taxane had worse PFS (HR, 1.69; 95 % CI, 1.19-2.40; adjusted P = 0.003) and OS (HR, 2.34; 95 % CI, 1.45-3.77; adjusted P = 0.0005). FOLR1 expression was lower in post-MIRV samples (n = 12; P = 0.005). New or worsening neuropathy was observed in 37.6 % of patients. Among the 34.1 % who experienced ocular toxicity, median onset was 42.5 days. Treatment was discontinued in 5.3 % of patients due to toxicity.
MIRV confers meaningful PFS benefit for a subset of individuals with HGSOC. Resistance may be associated with decreased FOLR1 target expression or payload resistance. FOLR1-targeted ADCs with a different payload should be evaluated for patients who progress on MIRV but retain high tumor FOLR1 expression.
mirvetuximab soravtansine-gynx（MIRV）是一种与叶酸受体1（FOLR1）结合的抗体药物偶联物（ADC），其携带微管抑制剂有效载荷。我们在一组复发/持续性高FOLR1表达的高级别浆液性卵巢癌（HGSOC）患者中研究了MIRV的疗效、毒性特征及耐药的决定因素。
这项回顾性研究纳入了170例复发/持续性FOLR1高表达（≥75%的肿瘤细胞具有≥2+膜染色强度）的HGSOC患者，这些患者接受了标准治疗的MIRV单药治疗。我们使用Kaplan-Meier方法和多变量Cox比例风险模型评估无进展生存期（PFS）和总生存期（OS）。我们使用CTCAE v5.0对不良事件进行分类。
总体而言，中位PFS为3.5个月（95%CI，3.0 - 4.1）。然而，22.4%的患者PFS≥6个月，且这些患者在先前基于紫杉烷的治疗期间或治疗后1个月内进展的可能性较小（P = 0.008）。先前接受紫杉烷治疗后出现进展的患者PFS较差（HR，1.69；95%CI，1.19 - 2.40；校正P = 0.003），OS也较差（HR，2.34；95%CI，1.45 - 3.77；校正P = 0.0005）。MIRV治疗后的样本（n = 12）中FOLR1表达较低（P = 0.005）。37.6%的患者出现了新的或加重的神经病变。在经历眼部毒性的患者中，34.1%的患者中位发病时间为42.5天。5.3%的患者因毒性而停药。
MIRV为一部分HGSOC患者带来了有意义的PFS获益。耐药可能与FOLR1靶点表达降低或有效载荷耐药有关。对于在MIRV治疗中进展但肿瘤FOLR1仍高表达的患者，应评估使用携带不同有效载荷的FOLR1靶向ADC。
