Patients randomized to abagovomab or placebo after platinum-taxane chemotherapy had identical median progression-free survival of 13.2 months.
Subgroup analysis failed to identify any patients who benefited from treatment with the antibody. Survival data are immature, but a preliminary analysis showed no difference between treatment groups at one year or three, Jacobus Pfisterer, MD, PhD, reported here at the European Society of Gynecological Oncology meeting.
"Abagovomab was able to induce a specific immunologic response (Ab3) soon after the induction period and was able to induce a nonspecific HAMA (human antimouse antibody) response," said Pfisterer, of Hospital Solingen in Germany.
"However, abagovomab maintenance treatment after debulking surgery and successful platinum and taxane first-line chemotherapy did not prolong progression-free survival in advanced ovarian cancer patients," he said.
Failure to improve survival in ovarian cancer has stimulated interest in maintenance therapy as a strategy to delay or prevent tumor relapse and thereby improve survival. Targeted specific immunotherapy has supporting rationale for use in this application, Pfisterer said.
Abagovomab is a murine anti-Ab1 antibody that recognizes CA125 and mimics the original antigen to induce a specific anti-CA125 immune response. Phase II studies of the antibody demonstrated induction of a specific response to CA125, which was associated with improved survival (Clin Cancer Res 2004; 10: 1500-1507, Ann Oncol 2006; 17: 1568-1577).
Abagovomab also was well tolerated, irrespective of treatment duration or route of administration (subcutaneous versus intramuscular), Pfisterer added.
The encouraging results from the preliminary trials provided the basis for a phase III, multicenter, randomized study of abagovomab in advanced ovarian cancer. Investigators in Europe and the U.S. enrolled patients with FIGO stage III-IV ovarian cancer treated surgically and with adjuvant platinum-taxane chemotherapy.
The trial included 870 patients, who were randomized 2:1 to abagovomab or placebo, and treatment continued until progression, development of unacceptable toxicity, or for 21 months after the last patient was enrolled.
Patients had screening CT at 10 weeks and then every 12 weeks. HAMA and Ab3 were measured at baseline and weeks 10, 22, 58, and 94.
The primary endpoint was progression-free survival, and the protocol required documentation of disease progression by CT or other imaging, as well as by clinical examination. Secondary objectives included overall survival, safety and tolerability, and time course of immune response and induction of HAMA and Ab3.
The patients had a mean age of 56, serous/papillary histology in 82% of cases, and ECOG performance status of 0-1 in all but two patients.
When the trial ended after a median follow-up of 28 months, 61% of patients in each group had progression events, resulting in a median progression-free survival of 13.2 months in each group.
Preliminary survival analysis showed that about 28% of the patients had died and that median overall survival had yet to be reached. One-year survival was about 94% and three-year survival was about 67% and was similar between treatment groups.
Ab3 response occurred as early as 10 weeks, and both Ab3 and HAMA responses were evident to the end of the study.
The type, frequency, and severity of adverse events was similar between treatment groups. The most common adverse events were injection-site reaction, fatigue, and arthralgia. Pfisterer reported that 4% of patients had grade 3 or higher adverse events.
The study was supported by the Menarini Group.
Pfisterer and multiple coinvestigators disclosed relationships with the Menarini Group and other commercial entities. Investigators in the trial included employees of Menarini Group.
- Reviewed by Vandana G. Abramson, MD Assistant Professor of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
European Society of Gynecological OncologySource Reference: Pfisterer J et al "Prospective, randomized phase-III study of Abagovomab as maintenance therapy in advanced ovarian cancer patients after complete response to first-line chemotherapy" ESGO 2011; Abstract 555.