Table 3.

Summary of efficacy and safety studies on vintafolide

Trial	PROCEED, NCT01170650, vintafolide with PLD versus PLD alone; Phase III	PRECEDENT, NCT00722592; vintafolide with PLD versus PLD alone; Phase II	NCT0050774I, vintafolide; Phase II
Design	Randomized, placebo-controlled	Randomized, open-label	Nonrandomized, single arm
Participants and schedule	n=640 (planned); adults; epithelial ovarian, fallopian tube, or primary peritoneal cancer; platinum-resistant; treatment with surgical debulking and platinum-based chemotherapy for primary disease prior to trial entry; patients screened with etarfolatide Randomized to vintafolide 2.5 mg IV on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle with PLD 50 mg/m2 every 4 weeks; or placebo IV on days 1,3,5, 15, 17, and 19 of a 4-week cycle with PLD 50 mg/m2 every 4 weeks Patients receive vintafolide until disease progression or toxicity	n=149; adults; epithelial ovarian, fallopian tube, or primary peritoneal cancer; platinum-resistant; treatment with surgical debulking and platinum-based chemotherapy for primary disease prior to trial entry; patients screened with etarfolatide for folate receptor status; randomized to vintafolide 2.5 mg IV on days 1, 3, 5, 15, 17, and 19 with PLD 50 mg/m2 on day 1 of a 4-week cycle; or PLD 50 mg/m2 on day 1 of a 4-week cycle only Patients receive vintafolide until disease progression or toxicity	n=47; adults; advanced epithelial ovarian cancer with serous or endometrioid histology or folate receptor-positive ovarian cancer, primary peritoneal cancer, or adenocarcinoma of the endometrium; treatment with platinum and/or taxane compounds prior to trial entry; patients screened with etarfolatide for folate receptor status Part A: induction phase, vintafolide 1.0 mg IV, Monday through Friday, for the first 3 weeks of each 4-week cycle; if no progression after 8 weeks, patients enter maintenance phase: vintafolide 2.5 mg IV, Monday, Wednesday, and Friday, weeks 1 and 3 of each 4-week cycle Patients receive vintafolide until disease progression, toxicity, or maximum benefit
Follow-up	Up to 26 months’ follow-up	Follow-up until rate for OS censoring reduces to 20%	Follow-up 2 years
Primary outcome	PFS	PFS	Clinical benefit; toxicity
Secondary outcomes	OS; quality of life; safety; adverse effects; objective response and disease control rate; duration of disease control and response	OS; safety and tolerability; objective response rate; duration of response	Tumor response; PFS; response duration; OS
Key results	Ongoing	Intention to treat analysis, for vintafolide with PLD versus PLD alone: PFS, 20 versus 10.8 weeks (P=0.031); PFS for patients with all tumor sites folate receptor positive, 24.0 versus 6.6 weeks (HR 0.381, P=0.018)	Clinical benefit observed in 7%, and disease control (CR + PR + SD) observed in 41.9%. Median PFS, 7.4 weeks, and median OS, 50.6 weeks. Median OS, 63.6 weeks in patients with all tumor sites folate receptor-positive, 41.7 weeks in patients with at least one tumor lesion folate receptor-positive, and 12.9 weeks in patients with no folate receptor-positive tumors
Adverse effects	Ongoing	Grade 3/4 adverse events occurring in greater than 10% patients included neutropenia, anemia, fatigue, and hand/foot syndrome; there was no reported statistical difference between study arms with regard to drug-related serious adverse events	Drug-related serious adverse events were observed in 14.3% patients, and included abdominal pain, constipation, ileus, nausea, and vomiting; the most common grade 3/4 adverse events were fatigue and constipation

Abbreviations: PFS, progression-free survival; OS, overall survival; PLD, PEGylated liposomal doxorubicin; CR, complete response; IV, intravenous; PR, partial response; SD, stable disease; HR, hazard ratio.