Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer Jonathan Berek, Peyton Taylor, William McGuire, L. Mary Smith, Birgit Schultes, and Christopher F. Nicodemus From the Stanford University School of Medicine, Stanford Cancer Center, Stanford, CA; University of Virginia, Charlottesville, VA; Franklin Square Hospital, Baltimore, MD; United Thera- peutics Corp, Research Triangle Park, NC; and Advanced Immune Therapeu- tics, Wellesley Hills, MA. Submitted April 29, 2008; accepted June 24, 2008; published online ahead of print at www.jco.org on December 22, 2008. Supported in part by Unither Inc. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Clinical Trials repository link available on JCO.org. Corresponding author: Jonathan S. Berek, MD, Division of Gynecologic Oncology, Stanford University School of Medicine, 300 Pasteur Dr, HH333, Stan- ford, CA 94305; e-mail: jberek@stanford.edu. © 2008 by American Society of Clinical Oncology 0732-183X/09/2703-418/$20.00 DOI: 10.1200/JCO.2008.17.8400 A B S T R A C T Purpose This phase III study tested the hypothesis that the CA-125–specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival. Patients and Methods Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point. Results Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively. Conclusion Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity. J Clin Oncol 27:418-425. © 2008 by American Society of Clinical Oncology INTRODUCTION Ovarian cancer remains a formidable challenge for the oncology community. The current standard of a platinum and taxane doublet after attempted complete surgical debulking was first established in 1996, 1 and further efforts to improve this have resulted in both amelioration and aggravation in toxicity but, to date, no definitive further improve- ment on this standard. 2 A recent Intergroup study 3 tested four triplet combinations with known activity and did not improve the progression-free overall survival. Paclitaxel monotherapy consolidation has produced variable results, 4-6 and primary intraperi- toneal therapy has improved survival relative to cisplatin and paclitaxel, 7 but this improved sur- vival has come at the cost of additional toxicity, leading to poor acceptance by many in the oncol- ogy community. This report is the final analysis of a multi- center clinical trial program designed to test a hypothesis generated in a subset analysis from a prior randomized maintenance immunotherapy study in ovarian cancer. 8 A population with quanti- fiable objective characteristics related to surgical outcome and CA-125 dynamics was selected as most likely to be able to translate a specific im- mune stimulation into a measurable clinical benefit in a double-blind, placebo-controlled, randomized trial setting. The agent oregovomab (OvaRex MAb B43.13; United Therapeutics Corpo- ration, Silver Spring, MD) is a high-affinity murine JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 27  NUMBER 3  JANUARY 20 2009 418 © 2008 by American Society of Clinical Oncology Downloaded from jco.ascopubs.org on November 13, 2014. For personal use only. No other uses without permission. Copyright © 2009 American Society of Clinical Oncology. All rights reserved.