Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome.
Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome.
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DOI：
10.1158/1078-0432.ccr-17-1434
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发表时间：
2017-10-01
期刊：
影响因子：
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通讯作者：
Awad MM
中科院分区：
文献类型：
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作者：
Nishino M;Dahlberg SE;Adeni AE;Lydon CA;Hatabu H;Jänne PA;Hodi FS;Awad MM
我们评估了接受商业PD-1抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者的肿瘤负荷动力学，以确定与改善总生存期（OS）相关的成像标志物。该研究包括160名晚期NSCLC患者，他们接受了商业nivolumab或pembrolizumab单药治疗作为临床护理的一部分。研究了肿瘤负荷动力学与OS的相关性。最佳总体缓解（BOR）时的肿瘤负荷变化范围为−100%至+278%（中位数：+3.5%）。有效率为18%（29/160）。当前和既往吸烟者的RR高于从未吸烟者（p=0.04）。在26例患者（16%）中观察到至少6个月的持久疾病控制，其中包括10例疾病稳定的BOR患者。使用里程碑分析，治疗8周内肿瘤负荷较基线增加<20%的患者的OS长于增加≥20%的患者（中位OS：12.4 vs. 4.6个月，p<0.001）。在调整吸烟（HR =0.86，p=0.61）和基线肿瘤负荷（HR=1.55，p= 0.062）后，整个治疗期间肿瘤负荷增加<20%的患者死亡风险显著降低（HR=0.24，考克斯p<0.0001），即使一些患者在治疗期间符合RECIST进展标准。1例患者（0.6%）出现与假进展一致的非典型缓解模式。在接受市售PD-1抑制剂治疗的晚期NSCLC患者中，24%的患者观察到客观缓解或持久疾病控制。治疗期间肿瘤负荷较基线增加<20%与OS较长相关，提出了治疗获益的实际标志物。在用PD-1抑制剂治疗的NSCLC中，假进展是罕见的。
We evaluated tumor burden dynamics in advanced non-small-cell lung cancer (NSCLC) patients treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS). The study included 160 advanced NSCLC patients treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS. Tumor burden change at best overall response (BOR) ranged from −100% to +278% (median: +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (p=0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with <20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS:12.4 vs. 4.6 months, p<0.001). Patients with <20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR=0.24, Cox p<0.0001) after adjusting for smoking (HR=0.86, p=0.61) and baseline tumor burden (HR=1.55, p=0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression. Objective response or durable disease control was noted in 24% of advanced NSCLC patients treated with commercial PD-1 inhibitors. A tumor burden increase of <20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors.