Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer

Objective. The primary purpose of this study was to determine if farletuzumab, an antifolate receptor-alpha monoclonal antibody, improved progression-free survival (PFS) versus placebo when added to standard chemo-therapy regimens in patients with platinum-sensitive recurrent ovarian cancer (OC) in first relapse (platinum-free interval: 6-36 months) with low cancer antigen 125 (CA-125) levels. Gynecologic Oncology (2023) Methods. Eligibility included CA-125 <= 3 x upper limit of normal (ULN, 105 U/mL), high-grade serous, platinum-sensitive recurrent OC, previous treatment with debulking surgery, and first-line platinum-based che-motherapy with 1st recurrence between 6 and 36 months since frontline platinum-based treatment. Patients re-ceived investigator's choice of either carboplatin (CARBO)/paclitaxel (PTX) every 3 weeks or CARBO/pegylated liposomal doxorubicin (PLD) every 4 weeks x6 cycles in combination with either farletuzumab [5 mg/kg weekly] or placebo randomized in a 2:1 ratio. Maintenance treatment with farletuzumab (5 mg/kg weekly) or placebo was given until disease progression or intolerance. Results. 214 patients were randomly assigned to farletuzumab+chemotherapy (142 patients) versus placebo +chemotherapy (72 patients). The primary efficacy endpoint, PFS, was not significantly different between treat-ment groups (1-sided alpha = 0.10; p-value = 0.25; hazard ratio [HR] = 0.89, 80% confidence interval [CI]: 0.71, 1.11), a median of 11.7 months (95% CI: 10.2, 13.6) versus 10.8 months (95% CI: 9.5, 13.2) for farletuzumab+che-motherapy and placebo+chemotherapy, respectively. No new safety concerns were identified with the combi-nation of farletuzumab+chemotherapy. Conclusions. Adding farletuzumab to standard chemotherapy does not improve PFS in patients with OC who were platinum-sensitive in first relapse with low CA-125 levels. Folate receptor-alpha expression was not measured in this study. (Clinical Trial Registry NCT02289950) (c) 2023 Published by Elsevier Inc.

Automated summary

The study aimed to determine the efficacy of farletuzumab, an antifolate receptor-alpha monoclonal antibody, in improving progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer. The results showed that adding farletuzumab did not improve PFS, and the expression of the folate receptor-alpha was not measured in this study.