PURPOSE: Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that 
binds to the folate receptor (FR), which is expressed on the majority of 
epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide 
combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The 
utility of an FR-targeted imaging agent, (99m)Tc-etarfolatide (EC20), in 
selecting patients likely to benefit from vintafolide was also examined.
PATIENTS AND METHODS: Women with recurrent platinum-resistant ovarian cancer who 
had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 
ratio to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without 
vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide 
scanning was optional. The primary objective was to compare progression-free 
survival (PFS) between the groups.
RESULTS: The intent-to-treat population comprised 149 patients. Median PFS was 
5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively 
(hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit 
was observed in patients with 100% of lesions positive for FR, with median PFS 
of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P 
= .013). The group of patients with FR-positive disease (10% to 90%) experienced 
some PFS improvement (HR, 0.873), whereas patients with disease that did not 
express FR experienced no PFS benefit (HR, 1.806).
CONCLUSION: Vintafolide plus PLD is the first combination to demonstrate an 
improvement over standard therapy in a randomized trial of patients with 
platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to 
benefit from vintafolide.