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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
  1. Thomas J. Herzog, MD,
  2. Elżbieta Kutarska, MD,
  3. Mariusz Bidzińsk, MD, PhD,
  4. Jim Symanowski, PhD,
  5. Binh Nguyen, MD, PhD,
  6. Reshma A. Rangwala, MD, PhD and
  7. R. Wendel Naumann, MD
  1. * University of Cincinnati Medical Center, Cincinnati, OH;
  2. Centrum Onkologii Ziemi Lubelskiej, Lublin; and
  3. Holycross Cancer Center, Kielce, Poland;
  4. § Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC;║Endocyte, Inc, West Lafayette, IN; and
  5. Merck & Co, Inc, Kenilworth, NJ.
  1. Address correspondence and reprint requests to Thomas J. Herzog, MD, University of Cincinnati Medical Center, UC Cancer Institute, 231 Albert Sabin Way, Suite 2005, Cincinnati, OH 45219. E-mail: thomas.herzog{at}


Objective 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.

Methods 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/m2 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%).

Results 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.

Conclusions 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.

  • Folate receptor
  • Ovarian cancer
  • Vintafolide

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