在低CA-125铂敏感型卵巢癌中，法乐妥珠单抗联合化疗对比安慰剂联合化疗的随机II期试验。
Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer.
作者信息
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, Vergote Ignace B
机构信息
University of Cincinnati Cancer Center, Cincinnati, OH, USA.
Instituto Nazionale Tumori di Napoli IRCCS, Fondazione Pascale (MITO), Napoli, Italy.
出版信息
Gynecol Oncol. 2023 Mar;170:300-308. doi: 10.1016/j.ygyno.2023.01.003. Epub 2023 Feb 7.
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).
目的
本研究的主要目的是确定在初次复发（铂类药物无治疗间隔时间为6 - 36个月）且癌抗原125（CA - 125）水平较低的铂敏感复发性卵巢癌（OC）患者中，抗叶酸受体 - α单克隆抗体法乐妥珠单抗添加至标准化疗方案后，与安慰剂相比是否能改善无进展生存期（PFS）。
方法
入选标准包括CA - 125≤3倍正常上限（ULN，105 U/mL）、高级别浆液性、铂敏感复发性OC、既往接受过减瘤手术治疗以及一线铂类化疗且自一线铂类治疗后6至36个月内首次复发。患者接受研究者选择的每3周一次的卡铂（CARBO）/紫杉醇（PTX）或每4周一次的CARBO/聚乙二醇脂质体阿霉素（PLD），共6个周期，并随机按2:1比例联合法乐妥珠单抗[5 mg/kg每周一次]或安慰剂。给予法乐妥珠单抗（5 mg/kg每周一次）或安慰剂进行维持治疗，直至疾病进展或出现不耐受。
结果
214例患者被随机分配至法乐妥珠单抗 + 化疗组（142例患者）和安慰剂 + 化疗组（72例患者）。主要疗效终点PFS在治疗组之间无显著差异（单侧α = 0.10；p值 = 0.25；风险比[HR] = 0.89，80%置信区间[CI]：0.71，1.11），法乐妥珠单抗 + 化疗组和安慰剂 + 化疗组的中位PFS分别为11.7个月（95%CI：10.2，13.6）和10.8个月（95%CI：9.5，13.2）。未发现法乐妥珠单抗 + 化疗联合用药有新的安全问题。
结论
在初次复发且CA - 125水平较低的铂敏感OC患者中，在标准化疗基础上加用法乐妥珠单抗并不能改善PFS。本研究未检测叶酸受体 - α表达情况。（临床试验注册号NCT02289950）
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