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Abagovomab did not prolong RFS, OS in ovarian cancer
The experimental monoclonal antibody abagovomab conferred no RFS or OS benefit in women with advanced ovarian cancer in first clinical remission, according phase 3 data from The MIMOSA Study.
The double blind, placebo-controlled, multicenter MIMOSA Study included 888 women with a mean age of 56.3 years. Eighty-two percent of women had stage III disease and 18% had stage IV disease; 81.5% had serous histology and 6.7% had endometrioid histology.
Investigators assigned 593 patients to receive 2 mg abagovomab (Menarini), and the other 295 patients received placebo. Treatment was administered once every 2 weeks for 6 weeks, then once every 4 weeks until recurrence or up to 21 months.
At baseline, 78.8% of participants had an ECOG status of zero and 20.9% had a performance status of 1. Standard deviation for mean exposure to treatment was 449.7 days.
Previous findings from phase 1 and 2 trials suggested an association between Ab3 production and OS in patients with advanced ovarian cancer who received abagovomab.
In the current study, data indicated the HR of RFS was 1.099 (95% CI, 0.919-1.315) among those assigned abagovomab, and the HR of OS was 1.150 (95% CI, 0.872-1.518). At final visit, researchers observed a robust response with a median anti-idiotypic antibody titer of 493,000 ng/mL.
Adverse events included injection site pain (50.2%), injection site erythema (25.6%) and fatigue (23.9%).
“Immunization using an anti-idiotypic approach targeting CA125 did not improve outcome in these patients,” Paul Sabbatini, MD, deputy physician-in-chief for clinical research at Memorial Sloan-Kettering Cancer Center, told HemOnc Today. “This occurred despite strong phase 2 evidence suggesting an association between antibody titers and overall survival. The study illustrates the need for randomized studies to define efficacy.”
Paul Sabbatini, MD, can be reached at Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: sabbatip@mskcc.org.
Disclosure: Sabbatini reports research support from Menarini Ricerche.
Perspective
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The use of maintenance chemotherapy after complete response to primary treatment to delay recurrence is compelling, but no studies to date have been able to demonstrate an OS benefit. Sabbatini and colleagues set out to investigate whether the immune response elicited by the use of abagovomab — an anti-idiotypic antibody generated against tumor-associated antigen CA-125 — as maintenance therapy could prolong survival.
Despite encouraging phase 1 and phase 2 data showing significantly improved OS for the patients who demonstrated an antibody response (23.56 vs 4.9 months) and robust immune responses in this study, this phase 3 trial failed to show an improvement in RFS, its primary outcome.
The study by Sabbatini and colleagues was well conducted and, despite negative results, it emphasizes the importance of confirming phase 2 data with larger, randomized controlled studies. Perhaps this means that immunotherapy should be part of the active treatment phase, where additional immune function could possibly improve the response to cytotoxic therapy? Or perhaps it could serve as a biomarker, where patients who do not mount an immune response should be given maintenance treatment with cytotoxic or targeted agents and those who are capable of mounting an immune response should not? Or maybe one target is not sufficient for a heterogeneous tumor, such as ovarian cancer?
As far as the benefit of maintenance therapy, GOG 212 — a phase 3-arm trial of maintenance chemotherapy vs. observation — is nearing completion, and we are anxious to find out whether maintenance chemotherapy could alter the natural course of ovarian cancer. Until then, the most important factor improving the outcome of our patients is primary/upfront tumor reductive surgery to no gross residual disease, followed by intraperitoneal chemotherapy.