Yuanyuan Zhang, Puneeth Iyengar, Steven Montalvo, Kenneth D Westover, Sawsan Rashdan, Kavitha Donthireddy, James Kim, Jonathan E Dowell, Benjamin Drapkin, Sheena Bhalla, Christian Chukwuma, Urooba Nadeem, Chul Ahn, Robert D Timmerman, David E Gerber
{"title":"关于PDL1未选择的III期非小细胞肺癌同期和巩固性杜瓦单抗与胸部放疗的安全性和有效性:简要报告。","authors":"Yuanyuan Zhang, Puneeth Iyengar, Steven Montalvo, Kenneth D Westover, Sawsan Rashdan, Kavitha Donthireddy, James Kim, Jonathan E Dowell, Benjamin Drapkin, Sheena Bhalla, Christian Chukwuma, Urooba Nadeem, Chul Ahn, Robert D Timmerman, David E Gerber","doi":"10.1016/j.ijrobp.2024.07.2333","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Consolidative durvalumab, an anti-programmed death ligand 1 (PDL1) immune checkpoint inhibitor, administered after concurrent chemoradiation improves outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) without substantially increasing toxicities. We studied a chemotherapy-free regimen of thoracic radiation therapy (RT) with concurrent and consolidative durvalumab.</p><p><strong>Methods and materials: </strong>This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received 2 cycles of durvalumab (1500 mg every 4 weeks) concurrently with thoracic RT (60 Gy in 30 fractions), followed by up to 13 cycles of consolidative durvalumab.</p><p><strong>Results: </strong>After 10 patients were enrolled, the trial was closed because of poor clinical outcomes. With a median follow-up of 12 months, 5 patients had disease progression and 8 patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including 1 grade 4 acute kidney injury during consolidation and 2 fatal pulmonary events. One fatal pulmonary event occurred during the concurrent phase in an active smoker; the other occurred after the first cycle of consolidative durvalumab. The primary endpoint of progression-free survival at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall survival was not reached, 10.5 months, and 7 months, for PDL1 ≥1%, <1%, and unavailable, respectively.</p><p><strong>Conclusions: </strong>In PDL1 unselected stage III NSCLC, thoracic RT plus concurrent and consolidative durvalumab is associated with high-grade toxicity and early disease progression.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":"68-74"},"PeriodicalIF":6.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Concerning Safety and Efficacy of Concurrent and Consolidative Durvalumab With Thoracic Radiation Therapy in PDL1-Unselected Stage III Non-Small Cell Lung Cancer: Brief Report.\",\"authors\":\"Yuanyuan Zhang, Puneeth Iyengar, Steven Montalvo, Kenneth D Westover, Sawsan Rashdan, Kavitha Donthireddy, James Kim, Jonathan E Dowell, Benjamin Drapkin, Sheena Bhalla, Christian Chukwuma, Urooba Nadeem, Chul Ahn, Robert D Timmerman, David E Gerber\",\"doi\":\"10.1016/j.ijrobp.2024.07.2333\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Consolidative durvalumab, an anti-programmed death ligand 1 (PDL1) immune checkpoint inhibitor, administered after concurrent chemoradiation improves outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) without substantially increasing toxicities. We studied a chemotherapy-free regimen of thoracic radiation therapy (RT) with concurrent and consolidative durvalumab.</p><p><strong>Methods and materials: </strong>This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received 2 cycles of durvalumab (1500 mg every 4 weeks) concurrently with thoracic RT (60 Gy in 30 fractions), followed by up to 13 cycles of consolidative durvalumab.</p><p><strong>Results: </strong>After 10 patients were enrolled, the trial was closed because of poor clinical outcomes. With a median follow-up of 12 months, 5 patients had disease progression and 8 patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including 1 grade 4 acute kidney injury during consolidation and 2 fatal pulmonary events. One fatal pulmonary event occurred during the concurrent phase in an active smoker; the other occurred after the first cycle of consolidative durvalumab. The primary endpoint of progression-free survival at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall survival was not reached, 10.5 months, and 7 months, for PDL1 ≥1%, <1%, and unavailable, respectively.</p><p><strong>Conclusions: </strong>In PDL1 unselected stage III NSCLC, thoracic RT plus concurrent and consolidative durvalumab is associated with high-grade toxicity and early disease progression.</p>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":\" \",\"pages\":\"68-74\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Oncology Biology Physics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijrobp.2024.07.2333\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Oncology Biology Physics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijrobp.2024.07.2333","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
简介在同期化疗后联合使用抗程序性死亡配体1(PDL1)免疫检查点抑制剂durvalumab可改善局部晚期非小细胞肺癌(NSCLC)患者的预后,且不会大幅增加毒性。我们研究了一种无化疗的胸腔放疗(RT)方案,并同时合并使用了durvalumab:这项单臂 II 期试验招募了 III 期 NSCLC 患者(无论肿瘤 PDL1 表达情况如何),患者表现为 ECOG 0-1,肺功能正常,RT 场符合标准器官限制条件。参与者在接受胸部RT(60 Gy,30次分次)的同时接受两个周期的durvalumab治疗(1500 mg,每4周一次),随后接受最多13个周期的durvalumab巩固治疗:10名患者入组之后,由于临床疗效不佳,试验结束。中位随访时间为12个月,5名患者病情恶化,8名患者死亡。6名患者发生了15起治疗相关的≥3级事件,包括1起巩固治疗期间的4级急性肾损伤和2起致命肺部事件。一起致命的肺部事件发生在一名活跃的吸烟者的同期治疗阶段;另一起发生在第一周期巩固性使用德伐卢单抗后。12个月无进展生存期(PFS)的主要终点为20%(PDL1≥1%为50%,PDL1不可用为0%)或结论:在未选择PDL1的III期NSCLC患者中,胸腔RT加同期和巩固性杜瓦单抗与高毒性和早期疾病进展有关。
Concerning Safety and Efficacy of Concurrent and Consolidative Durvalumab With Thoracic Radiation Therapy in PDL1-Unselected Stage III Non-Small Cell Lung Cancer: Brief Report.
Purpose: Consolidative durvalumab, an anti-programmed death ligand 1 (PDL1) immune checkpoint inhibitor, administered after concurrent chemoradiation improves outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) without substantially increasing toxicities. We studied a chemotherapy-free regimen of thoracic radiation therapy (RT) with concurrent and consolidative durvalumab.
Methods and materials: This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received 2 cycles of durvalumab (1500 mg every 4 weeks) concurrently with thoracic RT (60 Gy in 30 fractions), followed by up to 13 cycles of consolidative durvalumab.
Results: After 10 patients were enrolled, the trial was closed because of poor clinical outcomes. With a median follow-up of 12 months, 5 patients had disease progression and 8 patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including 1 grade 4 acute kidney injury during consolidation and 2 fatal pulmonary events. One fatal pulmonary event occurred during the concurrent phase in an active smoker; the other occurred after the first cycle of consolidative durvalumab. The primary endpoint of progression-free survival at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall survival was not reached, 10.5 months, and 7 months, for PDL1 ≥1%, <1%, and unavailable, respectively.
Conclusions: In PDL1 unselected stage III NSCLC, thoracic RT plus concurrent and consolidative durvalumab is associated with high-grade toxicity and early disease progression.
期刊介绍:
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.