Review Reinforces Safety, Efficacy of Mirvetuximab Soravtansine in Recurrent FRα-Positive Ovarian Cancer

A review and meta-analysis published in Critical Reviews in Oncology/Hematology found mirvetuximab soravtansine (Elahere; ImmunoGen) to have encouraging efficacy and a tolerable safety profile in patients with recurrent ovarian cancer with folate receptor alpha (FRα) expression.¹

AI image of microscope looking at ovarian cancer cells | Image credit: Justlight - stock.adobe.com

Mirvetuximab soravtansine, an FRα-directed antibody and microtubule inhibitor conjugate, is approved for the treatment of FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after 1 to 3 prior lines of therapy.² It was granted accelerated approval in 2022 based on promising data from Study 0417 (NCT04296890),³ with the confirmatory MIRASOL trial (NCT04209855) reinforcing the drug’s progression-free survival (PFS) and overall survival (OS) benefits along with its favorable safety profile compared with previous standards of care.⁴

While the data have been encouraging, the authors of the meta-analysis noted that most clinical trials were single-arm studies. Their meta-analysis aimed to assess all published studies to offer clinicians an evidence-based point of reference for the efficacy and safety of mirvetuximab soravtansine.¹

The researchers performed a comprehensive search of online databases—PubMed, Cochrane Library, and EMBASE—which delivered 191 publications. After removing duplicates and applying inclusion and exclusion criteria, a total of 7 studies involving 631 patients were included in the meta-analysis. Six of the studies were nonrandomized, and the remaining study was a randomized controlled study. A total of 49 patients had platinum-sensitive recurrence, 555 had platinum-resistant recurrence, and 27 had unclear grouping.

Every study included in the analysis reported the effective response of mirvetuximab soravtansine in recurrent ovarian cancer, but there was significant heterogeneity among the studies. Therefore, the overall response rate (ORR) for all recurrent forms of ovarian cancer was estimated using a random-effects model. The combined ORR was 0.36 (95% CI, 0.27-0.45).

ORR was also analyzed based on different recurrence types. The pooled ORR in platinum-sensitive, FRα-positive ovarian cancer was 0.57 (95% CI, 0.44-0.71), while the pooled ORR in platinum-resistant ovarian cancer was 0.29 (95% CI, 0.25-0.32). Among patients receiving mirvetuximab soravtansine with bevacizumab, the pooled ORR was 0.43 (95% CI, 0.36-0.50); those receiving mirvetuximab soravtansine alone had a pooled ORR of 0.24 (95% CI, 0.20-0.28).

Disease control rate (DCR) data were available in 4 studies, and the combined DCR was 0.88 (95% CI, 0.84-0.91). In the subgroup of patients with FRα-positive ovarian cancer receiving mirvetuximab soravtansine with bevacizumab, the combined DCR was 0.91 (95% CI, 0.87-0.96), compared with 0.82 (95% CI, 0.75-0.88) among patients receiving mirvetuximab soravtansine monotherapy.

A random-effect model was applied to 6 studies to determine median PFS, and the total effect value was a median PFS of 6.1 months (95% CI, 4.27-7.47). Among patients who had relapsed with platinum resistance, the pooled PFS was 6.26 months (95% CI, 4.67-7.85).

The most common adverse events (AEs) were blurred vision (0.45 [95% CI, 0.41-0.49]), nausea (0.42 [95% CI, 0.34-0.50]), and diarrhea (0.42 [95% CI, 0.31-0.52]). Hypertension (0.14 [95% CI, 0.09-0.20]), increased aspartate aminotransferase levels (0.02 [95% CI, 0.01-0.03]), and blurred vision (0.02 [95% CI, 0.01-0.03]) were the most common grade 3 or worse AEs.

The study was limited by heterogeneity in the analysis due to most selected papers being noncomparable and reporting phase 1 to 3 clinical investigations. Accessing the whole data for subgroup analyses was also difficult in some studies, and the authors noted that ORR and DCR are not adequate replacements for survival outcome indicators, including OS. More multicenter, real-world studies are needed to fill this gap, the authors said.

“To our knowledge, this urgently needed meta-analysis is the first to concentrate on the effectiveness of mirvetuximab soravtansine in recurrent ovarian cancer with FRα-positive expression,” the authors concluded. “This study found that mirvetuximab soravtansine is safe and effective for treating patients with recurrent ovarian cancer, especially when assessing the effectiveness of treatment for platinum-resistant ovarian cancer.” Still, more research is needed to evaluate mirvetuximab soravtansine monotherapy and combinations, they added.

References

1. Wang Y, Liu L, Jin X, Yu Y. Efficacy and safety of mirvetuximab soravtansine in recurrent ovarian cancer with FRa positive expression: a systematic review and meta-analysis. Crit Rev Onc Hematol. 2024;194:104230. doi:10.1016/j.critrevonc.2023.104230

2. Mirvetuximab soravtansine-gynx. Prescribing information. ImmunoGen; 2022. Accessed February 13, 2024. https://elahere.com/pdf/prescribing-information.pdf

3. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. News release. FDA. November 14, 2022. Accessed February 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant

4. Caffrey M. MIRASOL: Mirvetuximab soravtansine improves PFS, OS in certain women with recurrent ovarian cancer. AJMC. June 4, 2023. Accessed February 13, 2024. https://www.ajmc.com/view/mirasol-mirvetuximab-soravtansine-improves-pfs-os-in-certain-women-with-recurrent-ovarian-cancer