Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer
Thomas J Herzog 1 , Sandro Pignata 2 , Sharad A Ghamande 3 , Maria-Jesús Rubio 4 , Keiichi Fujiwara 5 , Christof Vulsteke 6 , Deborah K Armstrong 7 , Jalid Sehouli 8 , Robert L Coleman 9 , Hani Gabra 10 , Giovanni Scambia 11 , Bradley J Monk 12 , José A Arranz 13 , Kimio Ushijima 14 , Rabbie Hanna 15 , Claudio Zamagni 16 , Robert M Wenham 17 , Antionio González-Martín 18 , Brian Slomovitz 19 , Yan Jia 20 , Lisa Ramsay 20 , Krishnansu S Tewari 21 , Susan C Weil 20 , Ignace B Vergote 22
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).
CITATION Gynecol Oncol. 2023 Feb 7;170:300-308. doi: 10.1016/j.ygyno.2023.01.003.