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免疫治疗在晚期黑色素瘤和非小细胞肺癌中披荆斩棘取得重要成果的同时，PD-1抑制剂在头颈部鳞癌中也传来捷报，2016 ESMO大会上，CheckMate 141临床试验结果公布，在治疗复发或转移性头颈鳞癌中，Nivolumab能够保护功能并减轻患者症状。全面的研究结果同期在新英格兰医学杂志发表。
大多数头颈部鳞癌为局部晚期，超过50%会在3年内复发。对于铂类化疗后6个月内发生疾病进展的患者，中位生存时间≤6个月，且无有效治疗能延长生命。此类肿瘤有受到免疫攻击的易感性，因此可以尝试使用PD-1抑制剂进行治疗。
CheckMate 141是一项随机、开放标签的Ⅲ期临床研究，纳入361例铂类化疗难治的复发性头颈部肿瘤患者，按2:1比例随机接受Nivolumab治疗或标准化疗（甲氨蝶呤，多西他赛或西妥昔单抗）。主要终点是总生存（OS），次要终点包括无进展生存，客观缓解率，安全性和患者自我报告的生活质量。
研究结果显示，Nivolumab组患者的中位OS达到7.5个月，优于化疗组的5.1个月（HR=0.70），且在预计1年生存率方面前者也高出后者19%（36.0% vs 16.6%）；治疗第六个月的PFS率
分别为19.7% vs 9.9%，但两干预组的中位PFS差距不大（2.0 vs 2.3个月）。
本次ESMO大会上，研究者首次公布了患者自我报告的预后结果，包括功能能力和症状。这项分析纳入了完成问卷调查129例患者，问卷时间分别为基线，第9周和15周。问卷内容包括了患者功能如日常生活（工作等）的体能状态和情绪、认知以及社会福利。此外，还涉及其症状方面的问题，如疲劳，恶心，疼痛和呼吸短促。整体得分计入全球健康得分。每个治疗组的问卷结果均涵盖基线至9周和15周的结果。
对于接受Nivolumab治疗的患者，其身体功能和症状负担在治疗中未发生变化，部分甚至在第9和15周时相对于基线而言有所改善。另一方面，接受标准化疗的患者在第9和15周时，所有方面的得分都比基线水平更差。在第9周和15周的评分对比时可以发现，两个治疗组中Nivolumab为患者提供了显著的临床获益。
主要研究者，来自英国伦敦癌症研究所的资深临床肿瘤专家Kevin Harrington教授说：“比标准化疗相比，Nivolumab不仅能延长患者生命，还在维持功能和减轻症状方面发挥了作用。但是需要注意，Nivolumab治疗过程中可能会出现较为少见，但会对生活质量产生负面影响的不良反应。”
法国Beaujon大学医院内科肿瘤专家Sandrine Faivre教授在评论时表示：“这项研究采用了多种问卷来评估症状和生活质量，包括一个专为头颈部肿瘤患者量身定制的问卷。考虑到头颈部肿瘤预后的特殊性，这种做法显得尤为重要。例如，颈部肿瘤不仅引起疼痛，还会影响患者的饮食和言语功能，同时突出的外观也可能导致患者的社交孤立。”
“这是第一项能够表明免疫治疗除了延长生存期外，在改善生活质量和症状方面优于传统治疗的研究，Nivolumab可以在约三分之一的晚期头颈部肿瘤中起效，我们需要生物标志物或生物标准来识别可能从此种疗法中获益的患者，从而避免不必要的开支和副作用。” Faivre教授总结道。
信源：
1. Nivolumab Maintains Function and Reduces Symptoms in Relapsed Metastatic Head and Neck Cancer. ESMO 2016 Press Release.
2. Robert L. Ferris. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. October 9, 2016s.NEJM.
摘要原文
Abstract：LBA4
Title：Patient-Reported Outcomes (PROs) in Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treated with Nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141
Background: Patients (pts) with platinum-refractory R/M SCCHN have median survival ≤6 mo and suffer from their disease and its treatment. Accordingly, maintaining quality of life (QoL) is a key treatment goal. PRO data were collected as exploratory endpoints in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial comparing nivo to IC (methotrexate, docetaxel, or cetuximab) in 361 pts with platinum-refractory R/M SCCHN. We report the first comparative results for PRO for nivo and IC in R/M SCCHN.
Methods: The European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQ-H&N35), and EQ-5D were administered at baseline (BL), wk 9, and then at 6-wk intervals during treatment. A clinically relevant score change or difference was regarded as 10 points for the EORTC subscales. Analysis of covariance (ANCOVA) was applied to compare mean score changes between arms. Proportional hazards regression was used to evaluate time to clinically relevant score deterioration (TTD).
Results: BL questionnaire completion rates for nivo and IC were ~80% and ~75%, respectively. Low IC completion rates precluded analysis of mean differences after wk 15. Overall, 129 pts completed a PRO measure at BL and during follow up. Nivo significantly delayed TTD (P<0.05, 2-tailed) vs IC for global health; physical, role, cognitive, and social functioning; fatigue; dyspnea; and insomnia (EORTC QLQ-C30) as well as pain; sensory problems; and mouth opening problems (QLQ-H&N35). ANCOVA revealed statistically significant, clinically relevant differences favoring nivo at wks 9 and 15 for role and social functioning, fatigue, dyspnea, and appetite loss (EORTC QLQ-C30) as well as pain and sensory problems (QLQ-H&N35). Differences in mean values were observed for other PROs at wk 15 only.
Conclusions: Pts treated with nivo had delayed worsening of functioning and symptoms with PRO differences between arms favoring nivo up to ~4 mo of follow up. These results, as assessed through wk 15, suggest that pts receiving nivo maintained functioning for longer and had less pain, fatigue, and dyspnea on treatment as compared with IC.
