Rehim Shamsnur, Yuan Shuang, Wang Hongjing
Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
PLoS One. 2024 Dec 27;19(12):e0310736. doi: 10.1371/journal.pone.0310736. eCollection 2024.
Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed.
A systematic search (e.g., PubMed, Embase, Web Of Science, Cochrane Library) was conducted to identify all relevant clinical trials of MIRV alone or in combination with chemo- and/or target-therapies in solid tumors. The primary end-point was median progression-free survival (mPFS). The secondary endpoints were the Objective response rate (ORR) and adverse effects (AEs). A random-effects model was applied.
The study included nine research studies with a total of 682 patients. The pooled mPFS and pooled ORR were 6.70 months (95% CI 4.54-8.86, I2 = 96.21%) and 36% (95% CI: 28% to 44%, I2 = 76.79%), respectively. Significant differences were observed among intervention regimens and response to platinum. The pooled mPFS of MIRV monotherapy and MIRV+ Bevacizumab (BEV) combined therapy was 4.28 (95% CI 3.90-4.65, I2 = 0.00%) and 7.78 (95% CI 6.62-8.95, I2 = 0.00%), respectively. The pooled ORRs of MIRV monotherapy and MIRV+BEV combined therapy were 25% (95% CI 21%-29%, I2 = 25.20%) and 43% (95% CI 36%-50%, I2 = 0.01%), respectively. The pooled ORRs of the platinum-sensitive, platinum-resistant groups were 59% (95% CI 36%-81%, I2 = 61.88%), 33% (95% CI 25%-40%, I2 = 69.73%), respectively. In addition, we conducted supplementary subgroup analyses to explore the influence of FRα receptor expression levels and the number of prior treatments on treatment outcomes. The most common adverse effects were blurred vision (45.20%), nausea (40.13%), diarrhea (39.52%), fatigue (33.84%) and keratopathy (31.20%).
MIRV has significant therapeutic effects in solid tumors, especially when combined with BEV. In platinum-tolerant tumors, the efficacy of MIRV is also considerable. Overall, MIRV is relatively safe in solid tumors, and adverse reactions are relatively rare and mild.
Mirvetuximab Soravtansine（MIRV）是一种很有前景的抗体药物偶联物（ADC），靶向叶酸受体α（FRα），其在多种实体瘤中过表达。2022年11月，MIRV在美国被批准用于治疗接受过1 - 3线先前全身治疗方案的FRα阳性、铂耐药上皮性卵巢癌、输卵管癌或原发性腹膜癌的成年患者。因此，迫切需要关于其在不同癌症中疗效和安全性的高质量证据。
进行系统检索（如PubMed、Embase、Web of Science、Cochrane图书馆），以识别所有关于MIRV单独或与化疗和/或靶向治疗联合用于实体瘤的相关临床试验。主要终点是中位无进展生存期（mPFS）。次要终点是客观缓解率（ORR）和不良反应（AE）。应用随机效应模型。
该研究纳入了9项研究，共682例患者。汇总的mPFS和汇总的ORR分别为6.70个月（95%CI 4.54 - 8.86，I² = 96.21%）和36%（95%CI：28%至44%，I² = 76.79%）。在干预方案和对铂的反应之间观察到显著差异。MIRV单药治疗和MIRV + 贝伐单抗（BEV）联合治疗的汇总mPFS分别为4.28（95%CI 3.90 - 4.65，I² = 0.00%）和7.78（95%CI 6.62 - 8.95，I² = 0.00%）。MIRV单药治疗和MIRV + BEV联合治疗的汇总ORR分别为25%（95%CI 21% - 29%，I² = 25.20%）和43%（95%CI 36% - 50%，I² = 0.01%）。铂敏感组和铂耐药组的汇总ORR分别为59%（95%CI 36% - 81%，I² = 61.88%）、33%（95%CI 25% - 40%，I² = 69.73%）。此外，我们进行了补充亚组分析，以探讨FRα受体表达水平和先前治疗次数对治疗结果的影响。最常见的不良反应是视力模糊（45.20%）、恶心（40.13%）、腹泻（39.52%）、疲劳（33.84%）和角膜病变（31.20%）。
MIRV在实体瘤中具有显著的治疗效果，尤其是与BEV联合使用时。在铂耐受肿瘤中，MIRV的疗效也相当可观。总体而言，MIRV在实体瘤中相对安全，不良反应相对少见且轻微。
