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.