2016年12月4日-7日，第17届世界肺癌大会（WCLC）在奥地利维也纳盛大召开。在会议第4天（当地时间的7日上午）的免疫专场中，公布了4项重要免疫治疗研究成果。
来自西德尼Kimmel综合癌症中心的Julie Brahmer教授报告了KEYNOTE–024研究，详细阐述了研究中预先设定的探索性患者自我报告结局的分析结果。
研究背景
在KEYNOTE-024（NCT02142738）研究中，对于肿瘤细胞PD-L1表达≥50%（PD-L1肿瘤占比评分TPS≥50%），且无EGFR或ALK敏感突变的晚期非小细胞肺癌（NSCLC）患者，与以铂类为基础的化疗相比，一线应用PD-1抑制剂Pembrolizumab可以提供更优的无进展生存（PFS）改善。
尽管化疗组有44%的患者交叉进入免疫治疗组，Pembrolizumab仍显著改善了患者的总生存（OS,HR=0.60），且任何级别（73%vs 90%）的治疗相关不良事件和3-5级治疗相关不良事件（27%vs 53%）的发生率均比化疗少。
健康相关生活质量（Health-related quality of life,HRQoL）是抗肿瘤治疗中需要重点考虑的因素，特别是在一线治疗中。2016WCLC上，研究者报告了KEYNOTE-024研究中预先设定的探索性患者自我报告结局（Patient-Reported Outcomes,PRO）的分析结果。
研究内容
305例NSCLC患者随机分配进Pembrolizumab治疗（200mg,Q3W）或铂类双药化疗（研究者选择）；非鳞癌患者可选培美曲塞维持治疗。
在治疗1~3周期使用EORTC QLQ-C30量表和QLQ-LC13量表对患者进行生活质量调查，随后每9周调查一次。
主要的患者自我报告结局（PRO）终点是QLQ-C30全球健康状况/QoL评分自基线到第15周的变化，以及至QLQ-LC13（包括咳嗽、胸痛和呼吸困难）量表恶化的时间。
患者自我报告结局的分析对象包括所有接受过治疗并完成至少一次PRO调查的患者（n=299）。
研究结果
对于接受治疗的两组患者，基线时的PRO依从性＞90%，第15周时接近80%。
自基线至第15周，QLQ-C30全球健康状况/QoL评分的平均变化（最小二乘法）在Pembrolizumab治疗组（n=151）为6.95，而化疗组（n=148）则为-0.88，两者的差值达到7.82。
全球健康状况/QoL评分在第15周时的改善，Pembrolizumab治疗组和化疗组分别为40.0%vs 26.5%；Pembrolizumab治疗组QLQ-LC13评分恶化的患者人数占比少于后者（30%vs 39%），且恶化的时间推迟（HR=0.66）。
结论
Pembrolizumab治疗与含铂化疗相比，患者的HRQoL临床改善更有意义。结合Pembrolizumab在PFS和OS上的优势以及可管理的安全性，其或可作为PD-L1高表达晚期NSCLC患者一线治疗的重要选择。
摘要原文
KEYNOTE–024：Health–Related Quality of Life for Pembrolizumab vs Chemotherapy in Advanced NSCLC with PD–L1 TPS ≥50%
Background:
In KEYNOTE-024 (NCT02142738), pembrolizumab provided superior progression-free survival (PFS) over platinum-based chemotherapy as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression on ≥50% of tumor cells (ie, PD-L1 tumor proportion score [TPS] ≥50%) and no sensitizing EGFR or ALK aberrations (HR 0.50, P < 0.001). Despite a 44% crossover rate from chemotherapy to pembrolizumab, pembrolizumab also significantly improved overall survival (OS) (HR 0.60, P = 0.005). Any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related adverse events were less frequent with pembrolizumab. Health-related quality of life (HRQoL) is an important consideration for anticancer therapy, particularly in the first-line setting. We present data from the prespecified exploratory patient-reported outcomes (PRO) analysis of KEYNOTE-024.
Methods:
305 patients were randomized to pembrolizumab 200 mg Q3W or investigator-choice platinum-doublet chemotherapy plus optional pemetrexed maintenance therapy for nonsquamous disease. The EORTC QLQ-C30 and QLQ-LC13 were administered at cycles 1-3 and every 9 weeks thereafter. The key PRO end points were change from baseline to week 15 in the QLQ-C30 global health status/QoL score and time to deterioration in the QLQ-LC13 composite of cough, chest pain, and dyspnea. PROs were analyzed for all patients who received study treatment and completed ≥1 PRO instrument (n = 299).
Results:
Across treatment arms, PRO compliance was >90% at baseline and ~80% at week 15. Least squares (LS) mean (95% CI) change from baseline to week 15 in QLQ-C30 global health status/QoL score was 6.95 (3.29 to10.58) for pembrolizumab (n = 151) and –0.88 (–4.78 to 3.02) for chemotherapy (n = 148). The difference in LS means was 7.82 (95% CI 2.85-12.79; nominal 2-sided P = 0.002). The proportion of improved global health status/QoL score at week 15 was 40.0% for pembrolizumab and 26.5% for chemotherapy. Fewer patients in the pembrolizumab arm had deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30% vs 39%), and time to deterioration was also prolonged with pembrolizumab (HR 0.66, 95% CI 0.44-0.97; nominal 2-sided P = 0.029).
Conclusion:
Pembrolizumab was associated with a clinically meaningful improvement in HRQoL compared with platinum-based chemotherapy. Combined with the superior PFS and OS and manageable safety profile, these data suggest pembrolizumab may be a new standard of care for first-line treatment of PD-L1–expressing advanced NSCLC.
