A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1093/annonc/mdx439
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发表时间：
2017-11-01
影响因子：
50.5
通讯作者：
Licitra, L.
中科院分区：
文献类型：
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作者：
Bossi, P.;Miceli, R.;Licitra, L.
B490 (EudraCT# 2011-002564-24) 是一项随机、2b 期非劣效性研究，调查一线西妥昔单抗加顺铂加/不加紫杉醇（CetCis 与 CetCisPac）对复发性和/或转移性头颈鳞状细胞癌 (R/M SCCHN) 患者的疗效和安全性。符合条件的患者已确认R/M SCCHN（口腔/口咽/喉/下咽/鼻旁窦）且既往未接受过 R/M 疾病治疗。第 1 天给予西妥昔单抗（2 小时输注，400 mg/m(2)），然后每周给予（1 小时输注，250 mg/m(2)）。每个周期的第 1 天给予顺铂 1 小时输注（CetCis 组：100 mg/m(2)；CetCisPac 组：75 mg/m(2)），最多六个周期。每个周期的第 1 天，紫杉醇输注 3 小时（175 mg/m(2)）。六个周期后，给予西妥昔单抗维持治疗，直至疾病进展或出现不可接受的毒性。主要终点是无进展生存期（PFS）。我们假设与疗效相一致的非劣效界值为 1.40。共有 201 名患者按 1:1 随机分配至每种方案； 191 项可评估。使用 CetCis 的 PFS（中位，6 个月）不劣于使用 CetCisPac 的 PFS（中位，7 个月）[CetCis 与 CetCisPac 的 HR 0.99； 95% CI：0.72-1.36，P = 0.906；未达到非劣效性界限（90% CI 为 1.4）]。中位总生存期分别为 13 个月和 11 个月（HR = 0.77；95% CI：0.53-1.11，P = 0.117）。总缓解率分别为 41.8% 和 51.7%（OR = 0.69；95% CI：0.38-1.20，P = 0.181）。 CetCis 与 CetCisPac 的 a 级不良事件发生率分别为 76% 和 73%，而两种药物组与三种药物组的 4 级毒性较低（14% 与 33%，P = 0.015）。没有报告中毒性死亡或脓毒症，心脏事件可以忽略不计 (1%)。事实证明，两种药物 CetCis 方案的 PFS 不劣于带有 CetCisPac 的三种药物组合。两种方案的中位 OS 与 EXTREME 中观察到的相当，而危及生命的毒性发生率似乎有所降低。EudraCT# 2011-002564-24。
B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m(2)), then weekly (1-h infusions, 250 mg/m(2)). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m(2); CetCisPac arm: 75 mg/m(2)) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m(2)) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy.A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade a parts per thousand3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%).The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced.EudraCT# 2011-002564-24.