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.