Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial
Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial
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DOI：
10.1016/s0140-6736(09)60569-9
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发表时间：
2009-05-02
期刊：
影响因子：
168.9
通讯作者：
Hotko, Y.
中科院分区：
文献类型：
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作者：
Pirker, Robert;Pereira, Jose R.;Hotko, Y.
西妥昔单抗是一种靶向表皮生长因子受体（EGFR）的单克隆抗体，有可能提高晚期非小细胞肺癌患者的生存率。因此，我们比较了晚期egfr阳性非小细胞肺癌患者化疗加西妥昔单抗与单独化疗。方法：在一项多国、多中心、开放标签的III期临床试验中，经组织学或细胞学证实表达egfr的晚期非小细胞肺癌患者（>= 18岁）以1:1的比例随机分配到化疗加西妥昔单抗组或单纯化疗组。化疗方案为顺铂80mg /m（2)静脉输注，第1天，长春瑞滨25mg /m(2)静脉输注，每3周周期的第1天和第8天），最多6个周期。西妥昔单抗的起始剂量为400mg /m(2)，在第1天静脉输注超过2小时，从第8天开始，剂量为250mg /m(2)，每周超过1小时，在化疗结束后继续，直到疾病进展或出现不可接受的毒性。主要终点是总生存期。分析的目的是治疗。本研究已在ClinicalTrials.gov注册，注册号为NCT00148798。2004年10月至2006年1月，1125例患者被随机分配到化疗联合西妥昔单抗组（n=557）或单独化疗组（n=568）。化疗加西妥昔单抗组患者的生存时间比单独化疗组更长（中位11.3个月vs 10.1个月；死亡风险比0.871 [95% CI 0.762-0.996]; p=0.044）。西妥昔单抗相关的主要不良事件是痤疮样皮疹（548例中57例[10%]，3级）。西妥昔单抗加入铂基化疗为晚期非小细胞肺癌患者提供了一种新的治疗选择。
Background Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer.Methods In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (>= 18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m(2) intravenous infusion on day 1, and vinorelbine 25 mg/m(2) intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m(2) intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m(2) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798.Findings Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11.3 months vs 10.1 months; hazard ratio for death 0.871 [95% CI 0.762-0.996]; p=0.044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3).Interpretation Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer.