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

Gynecol Oncol. 2023 Mar:170:300-308. doi: 10.1016/j.ygyno.2023.01.003. Epub 2023 Feb 7.

Abstract

Objective: The primary purpose of this study was to determine if farletuzumab, an antifolate receptor-α monoclonal antibody, improved progression-free survival (PFS) versus placebo when added to standard chemotherapy 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.

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 chemotherapy with 1st recurrence between 6 and 36 months since frontline platinum-based treatment. Patients received 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 treatment groups (1-sided α = 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+chemotherapy and placebo+chemotherapy, respectively. No new safety concerns were identified with the combination 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-α expression was not measured in this study. (Clinical Trial Registry NCT02289950).

Keywords: Farletuzumab; Folate receptor-α; MORAb-003; Ovarian cancer; Progression-free survival.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CA-125 Antigen
  • Carboplatin
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Doxorubicin
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms, Glandular and Epithelial* / drug therapy
  • Ovarian Neoplasms* / drug therapy
  • Paclitaxel
  • Polyethylene Glycols
  • Recurrence

Substances

  • farletuzumab
  • CA-125 Antigen
  • Carboplatin
  • Paclitaxel
  • Doxorubicin
  • Polyethylene Glycols

Associated data

  • ClinicalTrials.gov/NCT02289950