Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer.
california; santa monica; Humans; Female; Ovarian Neoplasms; CA-125 Antigen; Neoplasms, Glandular and Epithelial; Carcinoma, Ovarian Epithelial; Carboplatin; Paclitaxel; Doxorubicin; Polyethylene Glycols; Recurrence; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local
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).
Women & Children
Obstetrics & Gynecology
Herzog, Thomas J; Pignata, Sandro; Ghamande, Sharad A; Rubio, Maria-Jesús; Fujiwara, Keiichi; Vulsteke, Christof; Armstrong, Deborah K; Sehouli, Jalid; Coleman, Robert L; Gabra, Hani; Scambia, Giovanni; Monk, Bradley J; Arranz, José A; Ushijima, Kimio; Hanna, Rabbie; Zamagni, Claudio; Wenham, Robert M; González-Martín, Antionio; Slomovitz, Brian; Jia, Yan; Ramsay, Lisa; Tewari, Krishnansu S; Weil, Susan C; and Vergote, Ignace B, "Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer." (2023). Articles, Abstracts, and Reports. 7119.