Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial
Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial
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DOI：
10.1093/annonc/mdz388
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发表时间：
2019-11-01
影响因子：
50.5
通讯作者：
Tang, P. Z.
中科院分区：
文献类型：
--
作者：
Guo, Y.;Ahn, M-J;Tang, P. Z.
背景：头颈鳞状细胞癌(HNSCC)经过一线铂类药物治疗后复发或转移的患者治疗选择有限，尤其是在亚洲国家。=18年，组织学或细胞学证实的HNSCC在一线铂治疗后复发/转移，不适合进行挽救手术或放射治疗，东部合作肿瘤组(ECOG)表现状态为0/1。患者被随机(2：1)接受口服阿法替尼(40 mg/d)或静脉注射甲氨蝶呤(40 mg/m(2)/周)，根据ECOG表现状况和既往EGFR靶向抗体治疗进行分层。主要终点是由一个独立的中央审查委员会对治疗分配盲目进行的无进展生存(PFS)评估。结果：总共有340名患者被随机分组(228名阿法替尼；112名甲氨蝶呤)。经过平均6.4月的随访期，与甲氨蝶呤相比，阿法替尼显著降低了进展/死亡风险37%(危险比0.63；95%可信区间0.48-0.82；P=0.0005；中位数2.9vs2.6个月；12周和24周的里程碑分析，58%vs41%，21%vs9%)。PFS的改善得到了生活质量方面的好处的补充。目的：阿法替尼有效率为28%，甲氨蝶呤有效率为13%。两组患者的总体存活率无显著差异。最常见的3级药物相关不良事件是皮疹/痤疮(阿法替尼为4%，甲氨蝶呤为0%)，腹泻(4%对0%)，疲劳(1%对5%)，贫血(
Background: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.Patients and methods: In this randomised, open-label, phase III trial, we enrolled Asian patients aged >= 18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2)/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.Results: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade >= 3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (