PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer.

Abstract

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.

• Authors: R Wendel Naumann, Robert L Coleman, Robert A Burger, Edward A Sausville, Elzbieta Kutarska, Sharad A Ghamande, Nashat Y Gabrail, Stephen E Depasquale, Elzbieta Nowara, Lucy Gilbert, Robert H Gersh, Michael G Teneriello, Wael A Harb, Panagiotis A Konstantinopoulos, Richard T Penson, James T Symanowski, Chandra D Lovejoy, Christopher P Leamon, David E Morgenstern, Richard A Messmann
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 35 Pg. 4400-6 (Dec 10 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 24127448 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• EC145
• EC20 folate peptide
• Oligopeptides
• Vinca Alkaloids
• liposomal doxorubicin
• Polyethylene Glycols
• Platinum
• Doxorubicin
• Folic Acid

Topics

• Administration, Intravenous
• Adult
• Aged
• Anemia (chemically induced)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Disease-Free Survival
• Doxorubicin (administration & dosage, adverse effects, analogs & derivatives, chemistry)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Fatigue (chemically induced)
• Female
• Folic Acid (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Nausea (chemically induced)
• Neutropenia (chemically induced)
• Oligopeptides (administration & dosage, adverse effects)
• Ovarian Neoplasms (drug therapy, pathology)
• Platinum (pharmacology)
• Polyethylene Glycols (administration & dosage, adverse effects, chemistry)
• Treatment Outcome
• Vinca Alkaloids (administration & dosage, adverse effects)