Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial
Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial
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DOI：
10.1016/s1470-2045(14)71200-8
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发表时间：
2015-02-01
期刊：
影响因子：
51.1
通讯作者：
VanderWalde, Ari
中科院分区：
文献类型：
--
作者：
Giralt, Jordi;Trigo, Jose;VanderWalde, Ari
背景我们的目的是比较帕尼单抗，一个完全人类单克隆抗体EGFR，加放化疗与未切除，局部晚期鳞状细胞癌患者的头和neck.Methods在这个国际，开放标签，随机，对照，2期试验，我们招募了患者局部晚期鳞状细胞癌的头和颈部从22个网站在全球8个国家。≥ 18岁的III、IVa或IVb期患者，既往未经治疗，可测量（至少一维>= 10 mm），局部晚期头颈部鳞状细胞癌（非鼻咽癌）和东部肿瘤协作组体能状态0-1随机分配（2：3）由独立供应商进行开放标签放化疗（放疗期间顺铂100 mg/m2两个周期）或放疗加帕尼单抗（帕尼单抗9 mg/kg，每3周一次，3个周期，与放疗联合给药），采用分层随机化，区组大小为5。所有患者均接受加速分割放射治疗，大体肿瘤70-72戈伊，亚临床病变54戈伊。主要终点是2年时的局部-区域控制，在所有随机分配的患者中进行分析，这些患者接受了至少一剂分配的方案特异性治疗（化疗、放疗或帕尼单抗）。审判已经结束，这是最后的分析。该研究注册于ClinicalTrials.gov，编号NCT 00547157。结果在2007年11月30日至2009年11月16日期间，152例患者入组，151例接受治疗（放化疗组61例，放疗加帕尼单抗组90例）。2年时，放化疗组的局部区域控制率为61%（95% CI 47-72），放疗加帕尼单抗组为51%（40-62）。最常见的3-4级不良事件是粘膜炎症（放化疗组62例患者中的25例[40%] vs放疗加帕尼单抗组89例患者中的37例[42%]），吞咽困难（20例[32%] vs 36例[40%]）和放射性皮肤损伤（7例[11%] vs 21例[24%]）。在放化疗组的62名患者中有25名（40%）和在放疗加帕尼单抗组的89名患者中有30名（34%）报告了严重不良事件。解释帕尼单抗不能在与放疗的联合治疗中取代顺铂用于未切除的III-IVb期头颈部鳞状细胞癌，EGFR抑制在局部晚期头颈部鳞状细胞癌中的作用需要重新评估。
Background We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck.Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (>= 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2: 3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m 2 during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157.Findings Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group.Interpretation Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed.