Farletuzumab Shows Limited Efficacy in Relapsed Ovarian Cancer
Farletuzumab, did not meet its primary endpoint in first platinum-sensitive relapse of ovarian cancer. But in a subset of patients, risk of progression was significantly reduced.
Maintenance farletuzumab following chemotherapy in combination with farletuzumab did not improve progression-free survival (PFS) for women with recurrent ovarian cancer, according to results from a study published in the Journal of Clinical Oncology.1
However, this global, multicenter, phase 3 study showed that risk for progression was reduced by 51% in a subset of patients with CA-125 not more than 3 times the upper limit of normal (ULN).
“These observations provide a dose-efficacy relationship for farletuzumab, and hence, proof of principle,” corresponding author Ignace Vergote, MD, chairman of the Leuven Cancer Institute, University Hospital Leuven, Belgium, told Cancer Therapy Advisor.
For women with epithelial ovarian cancer that has relapsed following initial response to a platinum-based regimen, treatment options are limited to further chemotherapy-based regimens.
“Despite a high initial response rate to first-line platinum doublet chemotherapy following surgical resection of EOC [epithelial ovarian cancer], there is an ongoing unmet need for improved treatment outcome,” the study investigators wrote.
Farletuzumab is a humanized monoclonal antibody against the folate receptor-alpha, which is expressed in 80% to 100% of epithelial ovarian cancers and is significantly absent in normal tissue. The study was undertaken following demonstrated antitumor activity in preclinical models of ovarian cancer and response rates seen in phase 2 studies.
Dr Vergote explained that the earlier phase 2 study, which provided initial observations on its efficacy, was small and might have overestimated the effect of farletuzumab, but added that it might still be effective.
RELATED: Phase 3 Binimetinib Trial in Ovarian Cancer Discontinued Due to Futility
MORab-003-004—the largest randomized trial in this population that attempted to expand treatment options for these women—was a double-blind, placebo-controlled study that involved 1100 women with epithelial ovarian tumors that relapsed after first-line treatment with platinum-based therapy. Patients were randomly assigned to placebo, farletuzumab 1.25 mg/kg, or farletuzumab 2.5 mg/kg administered once weekly in combination with the standard of care—6 cycles of carboplatin (area under the curve 5 to 6) and either paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 given intravenously every 3 weeks.
Following 6 weeks of combination therapy, patients continued to receive placebo, farletuzumab 1.25 mg/kg, or farletuzumab 2.5 mg/kg administered once weekly until disease progression as determined from modified Response Evaluation Criteria in Solid Tumors version 1.0.