Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody–drug conjugate Journal Article
| Authors: | Johannet, P.; Flint, M.; Chui, M. H.; Konner, J.; Friedman, C.; Green, A. K.; Guo, R.; Hensley, M. L.; Kyi, C.; Liu, Y.; Makker, V.; Rubinstein, M.; Sabbatini, P.; Tew, W. P.; Foote, M. B.; Weigelt, B.; Aghajanian, C.; Grisham, R. N.; O'Cearbhaill, R. E. |
| Article Title: | Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody–drug conjugate |
| Abstract: | Background: 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). Methods: 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. Results: 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; 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. Discussion: 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. © 2025 |
| Keywords: | resistance; antibody-drug conjugate; high-grade serous ovarian cancer; folr1; mirvetuximab soravtansine-gynx |
| Journal Title: | Gynecologic Oncology |
| Volume: | 195 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-04-01 |
| Start Page: | 173 |
| End Page: | 179 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2025.03.023 |
| PROVIDER: | scopus |
| PUBMED: | 40121972 |
| PMCID: | PMC12013361 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Roisin O'Cearbhaill -- Source: Scopus |
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