Study Reports No Overall Benefit of Adding Farletuzumab to Chemotherapy in Relapsed Ovarian Cancer, but Potential Subgroup Benefit Identified
Addition of the antifolate receptor-α antibody farletuzumab to carboplatin/taxane did not improve progression-free survival in patients with ovarian cancer in first platinum-sensitive relapse, reported Vergote et al in the Journal of Clinical Oncology. However, benefit was observed in patients with lower CA-125 levels and in those with higher farletuzumab exposure.
Study Details
In the phase III double-blind trial, 1,100 women with relapse at 6 to 24 months after initial surgery and platinum/taxane treatment from 274 sites in North America, Europe, the Asia Pacific region, Latin America, and Japan were randomly assigned to receive six cycles of carboplatin/taxane plus weekly farletuzumab at 1.25 mg/kg (n = 370) or 2.5 mg/kg (n = 366) or placebo (n = 364) until disease progression. The primary endpoint was progression-free survival.
Overall Results
Median progression-free survival was 9.5 months in the farletuzumab 1.25-mg/kg group (hazard ratio [HR] = 0.99, P = .9025) and 9.7 months in the 2.5-mg/kg group (HR = 0.86, P = .1521) vs 9.0 months in the placebo group. Median overall survival was 28.7 months (HR = 0.99, P = .9646) and 32.1 months (HR = 0.88, P = .3231) vs 29.1 months, respectively. The most common adverse events were mainly those associated with chemotherapy.
Subgroup Benefit
Among patients with baseline CA-125 levels ≤ 3 times the upper limit of normal (ULN), median progression-free survival was 10.0 months in the farletuzumab 1.25-mg/kg group (HR = 0.92, P = .7235) and 13.6 months in the 2.5-mg/kg group (HR = 0.49, P = .0028) vs 8.8 months in the placebo group, and median overall survival was not estimable (HR = 0.87, P = .6464) and not estimable (HR = 0.44, P = .0108) vs 29.1 months, respectively.
Patients with average minimum serum concentrations of farletuzumab above the median (HR = 0.679, P = .002) and those with area under the curve levels above the median (HR = 0.77, P = 0.012) had prolonged progression-free survival vs the placebo group.
The investigators concluded: “Neither farletuzumab dose met the study’s primary [progression-free survival] end point…. [S]ubgroup analyses demonstrated that patients with CA-125 levels not more than three times the ULN and patients with higher farletuzumab exposure showed superior [progression-free survival] and [overall survival] compared with placebo.”
They noted: “Based on the results of this phase III study, a follow-on study in patients… who have low CA-125 levels is planned using a modified farletuzumab dosing regimen.”
Morphotek, a subsidiary of Eisai Co, funded the study.
Ignace Vergote, MD, of University Hospitals Leuven, Belgium, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
