Adam Barsouk , Cole Friedes , Michelle Iocolano , Abigail Doucette , Roger B. Cohen , Kyle W. Robinson , Christopher A. D'Avella , Melina E. Marmarelis , John A. Kosteva , Aditi P. Singh , Christine A. Ciunci , William P. Levin , Keith A. Cengel , Jeffrey D. Bradley , Steven J. Feigenberg , Lova Sun , Charu Aggarwal , Corey J. Langer , Nikhil Yegya-Raman
{"title":"跃入太平洋：无法切除的 KRAS 基因突变非小细胞肺癌患者接受化疗和 Durvalumab 巩固治疗后的结果","authors":"Adam Barsouk , Cole Friedes , Michelle Iocolano , Abigail Doucette , Roger B. Cohen , Kyle W. Robinson , Christopher A. D'Avella , Melina E. Marmarelis , John A. Kosteva , Aditi P. Singh , Christine A. Ciunci , William P. Levin , Keith A. Cengel , Jeffrey D. Bradley , Steven J. Feigenberg , Lova Sun , Charu Aggarwal , Corey J. Langer , Nikhil Yegya-Raman","doi":"10.1016/j.cllc.2023.12.009","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span><span>Immune checkpoint inhibitor (ICI) consolidation following concurrent </span>chemoradiotherapy<span><span> (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable </span>NSCLC. </span></span><em>KRAS</em> mutation may influence response to ICI.</p></div><div><h3>Methods</h3><p><span>In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable </span><em>KRAS</em> mutated (<em>KRAS</em>-mt) and wild-type (<em>KRAS</em>-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan–Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all <em>KRAS</em>-mt patients and <em>KRAS-G12C-</em>mutated patients. Outcomes were also compared with and without ICI consolidation.</p></div><div><h3>Results</h3><p>Of 156 patients, 42 (26.9%) were <em>KRAS</em>-mt and 114 (73.1%) were <em>KRAS</em>-wt. Baseline characteristics differed only in histology; <em>KRAS</em>-mt NSCLC more likely to be adenocarcinoma. <em>KRAS</em>-mt patients had worse PFS (median 6.3 vs. 10.7 months, <em>P</em> = .041) but similar OS (median 23.1 vs. 27.3 months, <em>P</em> = .237). <em>KRAS</em><span>-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, </span><em>P</em> = .007). Among patients who received ICI (n = 114), <em>KRAS</em>-mt was not associated with inferior PFS (8.1 vs. 11.9 months, <em>P</em> = .355) or OS (30.5 vs. 31.7 months, <em>P</em> = .692). <em>KRAS-G12C</em> patients (n = 22) had similar PFS and OS to other <em>KRAS</em>-mt.</p></div><div><h3>Conclusion</h3><p>In one of the largest post-CRT <em>KRAS</em>-mt cohort published, <em>KRAS</em>-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of <em>KRAS</em>-mt status.</p></div>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plunging Into the PACIFIC: Outcomes of Patients With Unresectable KRAS-Mutated Non-Small Cell Lung Cancer Following Definitive Chemoradiation and Durvalumab Consolidation\",\"authors\":\"Adam Barsouk , Cole Friedes , Michelle Iocolano , Abigail Doucette , Roger B. Cohen , Kyle W. Robinson , Christopher A. D'Avella , Melina E. Marmarelis , John A. Kosteva , Aditi P. Singh , Christine A. Ciunci , William P. Levin , Keith A. Cengel , Jeffrey D. Bradley , Steven J. Feigenberg , Lova Sun , Charu Aggarwal , Corey J. Langer , Nikhil Yegya-Raman\",\"doi\":\"10.1016/j.cllc.2023.12.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span><span>Immune checkpoint inhibitor (ICI) consolidation following concurrent </span>chemoradiotherapy<span><span> (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable </span>NSCLC. </span></span><em>KRAS</em> mutation may influence response to ICI.</p></div><div><h3>Methods</h3><p><span>In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable </span><em>KRAS</em> mutated (<em>KRAS</em>-mt) and wild-type (<em>KRAS</em>-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan–Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all <em>KRAS</em>-mt patients and <em>KRAS-G12C-</em>mutated patients. Outcomes were also compared with and without ICI consolidation.</p></div><div><h3>Results</h3><p>Of 156 patients, 42 (26.9%) were <em>KRAS</em>-mt and 114 (73.1%) were <em>KRAS</em>-wt. Baseline characteristics differed only in histology; <em>KRAS</em>-mt NSCLC more likely to be adenocarcinoma. <em>KRAS</em>-mt patients had worse PFS (median 6.3 vs. 10.7 months, <em>P</em> = .041) but similar OS (median 23.1 vs. 27.3 months, <em>P</em> = .237). <em>KRAS</em><span>-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, </span><em>P</em> = .007). Among patients who received ICI (n = 114), <em>KRAS</em>-mt was not associated with inferior PFS (8.1 vs. 11.9 months, <em>P</em> = .355) or OS (30.5 vs. 31.7 months, <em>P</em> = .692). <em>KRAS-G12C</em> patients (n = 22) had similar PFS and OS to other <em>KRAS</em>-mt.</p></div><div><h3>Conclusion</h3><p>In one of the largest post-CRT <em>KRAS</em>-mt cohort published, <em>KRAS</em>-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of <em>KRAS</em>-mt status.</p></div>\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1525730423002668\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1525730423002668","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0
摘要
背景在PACIFIC试验中，免疫检查点抑制剂（ICI）在同时进行化放疗（CRT）后的巩固治疗大大改善了PFS和OS，成为局部晚期、不可切除NSCLC的标准治疗方法。KRAS突变可能会影响对ICI的反应。方法在这项单一机构的回顾性分析中，我们比较了2017年10月至2021年12月期间接受CRT治疗的不可切除的KRAS突变型（KRAS-mt）和野生型（KRAS-wt）NSCLC患者的治疗结果。对所有KRAS-mt患者和KRAS-G12C突变患者完成放疗后的mPFS和mOS进行了卡普兰-梅耶分析比较。结果 在156例患者中，42例（26.9%）为KRAS-mt患者，114例（73.1%）为KRAS-wt患者，基线特征仅在组织学方面存在差异；KRAS-mt NSCLC更可能是腺癌。KRAS-mt患者的PFS较差（中位6.3个月对10.7个月，P=0.041），但OS相似（中位23.1个月对27.3个月，P=0.237）。KRAS-mt患者更有可能因CRT后疾病快速进展而未接受ICI治疗（23.8% vs 4.4%，P=0.007）。在接受 ICI 的患者（n=114）中，KRAS-mt 与较差的 PFS（8.1 个月 vs 11.9 个月，p=0.355）或 OS（30.5 个月 vs 31.7 个月，p=0.692）无关。结论 在已发表的最大规模的CRT后KRAS-mt队列中，KRAS-mt与较差的PFS相关，主要是由于ICI巩固治疗前的快速进展，但不影响OS。Micro-AbstractWe present one of the largest, real-world KRAS-mutated cohorts following chemoradiation and durvalumab consolidation (per the PACIFIC trial) in unresectable, locally-advanced NSCLC, comparing 42 KRAS-mt and 114 patients KRAS-wt patients.在接受 ICI 巩固治疗的患者中，无论 KRAS-mt 状态如何，疗效都相当。我们发现，KRAS-mt 患者更有可能在开始使用杜伐单抗前病情持续进展；但是，在接受杜伐单抗巩固治疗的患者中，PFS 和 OS 与 KRAS-wt 相似。
Plunging Into the PACIFIC: Outcomes of Patients With Unresectable KRAS-Mutated Non-Small Cell Lung Cancer Following Definitive Chemoradiation and Durvalumab Consolidation
Background
Immune checkpoint inhibitor (ICI) consolidation following concurrent chemoradiotherapy (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable NSCLC. KRAS mutation may influence response to ICI.
Methods
In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable KRAS mutated (KRAS-mt) and wild-type (KRAS-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan–Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all KRAS-mt patients and KRAS-G12C-mutated patients. Outcomes were also compared with and without ICI consolidation.
Results
Of 156 patients, 42 (26.9%) were KRAS-mt and 114 (73.1%) were KRAS-wt. Baseline characteristics differed only in histology; KRAS-mt NSCLC more likely to be adenocarcinoma. KRAS-mt patients had worse PFS (median 6.3 vs. 10.7 months, P = .041) but similar OS (median 23.1 vs. 27.3 months, P = .237). KRAS-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, P = .007). Among patients who received ICI (n = 114), KRAS-mt was not associated with inferior PFS (8.1 vs. 11.9 months, P = .355) or OS (30.5 vs. 31.7 months, P = .692). KRAS-G12C patients (n = 22) had similar PFS and OS to other KRAS-mt.
Conclusion
In one of the largest post-CRT KRAS-mt cohort published, KRAS-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of KRAS-mt status.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
