Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial
Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial
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DOI：
10.1001/jamaoncol.2019.1478
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发表时间：
2019-09-01
期刊：
影响因子：
28.4
通讯作者：
Baas, Paul
中科院分区：
文献类型：
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作者：
Theelen, Willemijn S. M. E.;Peulen, Heike M. U.;Baas, Paul
这项2期随机临床试验评估了立体定向体部放疗后pembrolizumab与单独pembrolizumab是否能增强转移性非小细胞肺癌患者的肿瘤反应。Key PointsDistance立体定向体部放疗是否能通过增加转移性非小细胞肺癌患者非放疗肺癌病灶的肿瘤反应来增强免疫检查点抑制的效果？结果：在这项2期临床试验中，76例复发转移性非小细胞肺癌患者随机接受单用派姆单抗或派姆单抗立体定向体部放疗后治疗，对照组12周的总有效率为18%，实验组为36%。尽管观察到总反应率加倍，但结果不符合有意义的临床益处的研究标准。重要性许多接受免疫治疗的晚期非小细胞肺癌（NSCLC）患者显示原发性耐药。高剂量放疗可导致肿瘤抗原释放增加、抗原呈递改善和T细胞浸润。这种放射疗法可能会增强检查点抑制的效果。目的评估在派姆单抗治疗前对单个肿瘤部位进行立体定向体部放疗是否能增强转移性NSCLC患者的肿瘤反应。多中心、随机、II期研究（PEMBRO-RT），纳入了2015年7月1日至2018年3月31日期间入组的92例晚期NSCLC患者，不考虑程序性死亡配体1（PD-L1）状态。数据分析是意向治疗人群。干预Pembrolizumab（200 mg/kg，每3周一次）单独给药（对照组）或在放疗（3次剂量，每次8戈伊）后给药（实验组）至单个肿瘤部位，直至确认放射学进展、不可接受的毒性作用、研究者决定、患者撤回知情同意或最长24个月。主要结局和指标12周时总缓解率（ORR）从对照组的20%提高到试验组的50%，P
This phase 2 randomized clinical trial assesses whether pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone enhances tumor response in patients with metastatic non-small cell lung cancer.Key PointsQuestionDoes stereotactic body radiotherapy enhance the effect of immune checkpoint inhibition by increasing tumor response in nonirradiated lung cancer lesions in metastatic non-small cell lung cancer? FindingsIn this phase 2 clinical trial of 76 patients with recurrent metastatic non-small cell lung cancer randomized to either pembrolizumab alone or pembrolizumab after stereotactic body radiotherapy on a single tumor site, the overall response rate at 12 weeks was 18% in the control arm vs 36% in the experimental arm. MeaningStereotactic body radiotherapy prior to pembrolizumab was well tolerated; although a doubling of the overall response rate was observed, the results did not meet the study criteria for meaningful clinical benefit.ImportanceMany patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy show primary resistance. High-dose radiotherapy can lead to increased tumor antigen release, improved antigen presentation, and T-cell infiltration. This radiotherapy may enhance the effects of checkpoint inhibition. ObjectiveTo assess whether stereotactic body radiotherapy on a single tumor site preceding pembrolizumab treatment enhances tumor response in patients with metastatic NSCLC. Design, Setting, and ParticipantsMulticenter, randomized phase 2 study (PEMBRO-RT) of 92 patients with advanced NSCLC enrolled between July 1, 2015, and March 31, 2018, regardless of programmed death-ligand 1 (PD-L1) status. Data analysis was of the intention-to-treat population. InterventionsPembrolizumab (200 mg/kg every 3 weeks) either alone (control arm) or after radiotherapy (3 doses of 8 Gy) (experimental arm) to a single tumor site until confirmed radiographic progression, unacceptable toxic effects, investigator decision, patient withdrawal of consent, or a maximum of 24 months. Main Outcomes and MeasuresImprovement in overall response rate (ORR) at 12 weeks from 20% in the control arm to 50% in the experimental arm with P