title: Adverse Event Profile by Folate Receptor Status for Vintafolide and Pegylated Liposomal Doxorubicin in Combination, Versus Pegylated Liposomal Doxorubicin Alone, in Platinum-Resistant Ovarian Cancer: Exploratory Analysis of the Phase II PRECEDENT Trial.
abstract: This exploratory analysis evaluated the incidence of adverse events (AEs) by folate receptor (FR) status in the randomized, multicenter, open-label PRECEDENT study in women with platinum-resistant ovarian cancer receiving pegylated liposomal doxorubicin (PLD) ± the small-molecule drug conjugate vintafolide.
  
  
  
  Women 18 years or older with platinum-resistant ovarian cancer were randomized 2:1 to vintafolide (2.5 mg intravenously, 3 times per week, weeks 1 and 3, every 28 days) + PLD (50 mg/m intravenously, day 1, every 28 days) or PLD alone (same dose/schedule). The expression of functionally active FR was evaluated by single-photon emission computed tomography with etarfolatide. Patients were categorized according to FR positivity: patients with all target lesions positive for FR expression (FR 100%), patients with 1 or more but not all target lesions positive for FR expression (FR 10%-90%), and patients with all lesions negative for FR expression (FR 0%).
  
  
  
  Data on FR status were available for 94 patients: 38 were FR 100%, 36 were FR 10% to 90%, and 20 were FR 0%. Across all FR subgroups, the duration of treatment was longer, and the number of cycles was higher in combination-therapy arms than PLD-alone arms. Although the frequency of AEs was relatively consistent across subgroups, the FR 100% subgroup had a higher incidence of patients with at least 1 AE for combination therapy versus PLD alone. No surprising safety signals were shown according to FR status. The incidence of grade 3 or 4 treatment-emergent drug-related AEs was generally low across all FR subgroups and treatment arms.
  
  
  
  This exploratory analysis suggests that FR status does not influence the AE profile of vintafolide + PLD combination therapy or PLD alone in patients with platinum-resistant ovarian cancer. Future a priori analyses in larger populations are needed to confirm these findings.
authors.affiliation: *University of Cincinnati Medical Center, Cincinnati, OH; †Centrum Onkologii Ziemi Lubelskiej, Lublin; and ‡Holycross Cancer Center, Kielce, Poland; §Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC;║Endocyte, Inc, West Lafayette, IN; and ¶Merck & Co, Inc, Kenilworth, NJ.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kutarska
authors.forename: Mariusz
authors.initials: M
authors.lastname: Bidzińsk
authors.forename: Jim
authors.initials: J
authors.lastname: Symanowski
authors.forename: Binh
authors.initials: B
authors.lastname: Nguyen
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Rangwala
authors.forename: R Wendel
authors.initials: RW
authors.lastname: Naumann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D058972:Folic Acid Transporters / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000903:Antibiotics, Antineoplastic; C520389:EC145; D058972:Folic Acid Transporters; D014748:Vinca Alkaloids; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid