Western Regional Blog – BC, YK, AB, NWT and Nunavut
Vintafolide binds to the folate receptor, a molecule that is expressed on the majority of ovarian cancers. When added to pegylated liposomal doxorubicin in this 149-patient trial, it improved median progression-free survival from 2.7 to 5.0 months. The data also suggested that folate receptor expression could be used as a biomarker predictive of benefit from this novel compound.
J. Clin. Oncol 2013 Oct 14; [EPub Ahead of Print], RW Naumann, RL Coleman, RA Burger, EA Sausville, E Kutarska, SA Ghamande, NY Gabrail, SE Depasquale, E Nowara, L Gilbert, RH Gersh, MG Teneriello, WA Harb, PA Konstantinopoulos, RT Penson, JT Symanowski, CD Lovejoy, CP Leamon, DE Morgenstern, RA Messmann
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, 99mTc-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/m2 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.