From trials to the clinic: Real-world experience with mirvetuximab soravtansine in platinum-resistant ovarian cancer and the "Lazarus effect.

Abstract

e17579 Background: Platinum-resistant ovarian cancer (PROC) has limited treatment options, with response rates of 10–15% and median progression-free survival (PFS) of ~ 3.5 months. Mirvetuximab soravtansine (MIRVE), a folate receptor alpha (FRα-)directed antibody-drug conjugate, is the first targeted therapy approved for FRα-positive PROC. This single-center real-world study reports on its effectiveness and safety, including a unique case demonstrating a ‘Lazarus effect’ and stable brain metastases. Methods: Seventeen FRα+ PROC patients treated with MIRVE at the University Hospital of Florence (February-December 2025) were retrospectively analyzed. Data included prior therapies, FRα expression, PFS, response, and toxicity (CTCAE v5.0). PFS was defined as time from treatment initiation to progression or last follow-up. FOLR1 positivity was defined as ≥75% of viable tumor cells with moderate (2+) or strong (3+) membrane staining.Primary objectives were real-world effectiveness and safety; secondary objectives included factors associated with response and toxicity characterization. Results: The median patient age was 60.5 years (range 39–80). Patients were heavily pretreated: 35% had received more than two prior lines of therapy, 53% more than three, and 12% received MIRVE in the first-line platinum-resistant setting. FRα expression was histologically scored as 2+ in 3 patients(18%), and 3+ in 14 patients (82%). Median PFS was 3 months (range 1–10), with 8 progression events and 9 censored observations at the time of analysis. Grade ≥3 treatment-related adverse events occurred in 6% of patients (peripheral neuropathy). Grade 1–2 toxicities included ocular events (24%), neurotoxicity (35%), neutropenia (12%), and thrombocytopenia (6%). One patient harboring BRCA1 mutation and FRα 3+, previously treated with first-line carboplatin plus paclitaxel followed by olaparib maintenance and second-line carboplatin plus gemcitabine, achieved near-complete hepatic response, a partial response at other disease sites, and stable brain metastases. This exceptional clinical benefit was consistent with a marked “Lazarus effect” and was associated with a progression-free survival of 10 months. This patient also experienced the only grade 3 treatment-related toxicity (neuropathy), which led to treatment discontinuation. Conclusions: Mirvetuximab Soravtansine demonstrated a manageable safety and PFS outcomes consistent with those reported in clinical trials. High FRα expression (3+) correlated with improved clinical outcomes. Notably, the association of the most severe treatment-related toxicity with exceptional response suggests a potential association between higher-grade adverse events and therapeutic benefit. These real-world data complement data from pivotal trials and provide clinically relevant insights for patient management.