在罕见肿瘤中进行抗 CTLA-4 和抗 PD-1 双重阻断的 II 期试验 SWOG/NCI 经验:浸润性粘液性或非粘液性肺鳞状腺癌(原支气管肺泡癌)。

IF 4.3 2区 医学 Q2 ONCOLOGY
Therapeutic Advances in Medical Oncology Pub Date : 2024-11-22 eCollection Date: 2024-01-01 DOI:10.1177/17588359241293401
Young Kwang Chae, Megan Othus, Sandip Pravin Patel, David E Gerber, Tawee Tanvetyanon, Hye Sung Kim, Liam Il-Young Chung, Christine M McLeod, Gabby Lopez, Helen X Chen, Elad Sharon, Howard Streicher, Cristopher W Ryan, Charles D Blanke, Razelle Kurzrock
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引用次数: 0

摘要

背景:抗程序性死亡-1(PD-1)/细胞毒性T淋巴细胞抗原-4抗体对多种恶性肿瘤具有疗效:抗程序性死亡-1(PD-1)/细胞毒性T淋巴细胞抗原-4抗体对多种恶性肿瘤具有疗效:本研究首次展示了ipilimumab-nivolumab治疗肺部浸润性粘液性或非粘液性鳞状腺癌(分别为浸润性粘液性腺癌(IMA)或浸润性非粘液性鳞状腺癌(INLA))的结果:设计:罕见肿瘤中的双抗CTLA-4和抗PD-1阻断疗法(DART)是一项前瞻性、开放标签、多中心(1016个美国站点)、多队列的II期试验,采用伊匹单抗(1毫克/千克,静脉注射,每6周一次)加尼维单抗(240毫克,静脉注射,每2周一次):方法:组织学诊断为晚期IMA或INLA的参与者被纳入支气管肺泡癌队列,这些参与者至少对一种疗法无应答。主要终点是根据实体瘤反应评价标准得出的总反应率(ORR)(证实完全和部分反应(CR和PR))。次要终点是无进展生存期(PFS)、总生存期(OS)、临床获益率(CBR;疾病稳定期(SD)⩾ 6 个月加 ORR)和毒性:8名可评估患者(中位年龄:77岁;既往治疗次数从0到4次不等;1名患者既往接受过PD-1抑制剂治疗;包括6名IMA患者和2名INLA患者)接受了治疗。其中一名 IMA 患者的病情缓解率为 40%(PFS 45.2+ 个月,PD-L1 0%,KRAS G12C 突变,肿瘤突变负荷 [TMB] 13 突变/Mb)。一名 INLA 患者的生存期缩短了 66%(PFS 23.8 个月,PD-L1 未知,无可操作性突变,TMB 3 突变/Mb)。总体ORR为25.0%(2/8),CBR为62.5%(5/8);SD大于6个月的患者的PFS分别为43.4+、11.7+和8.3个月。中位 PFS 为 16 个月(5.3 个月未达标),中位 OS 为 32.2 个月(14.6 个月未达标)。毒性情况与之前的报告相似:结论:在支气管肺泡癌队列(IMA、INLA)中,伊匹单抗联合尼妥珠单抗的持久ORR为25.0%,CBR为62.5%(PFS, 8.3 11.7+.23.8(PR)、43.4+ 和 45.2+(PR)个月)。目前正在进行相关研究,以确定反应和耐药性标志物。试验注册:试验注册:ClinicalTrials.gov 注册:NCT02834013.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Phase II trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors SWOG/NCI experience: invasive mucinous or non-mucinous lepidic adenocarcinoma of the lung (formerly bronchioloalveolar carcinoma).

Background: Anti-programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 antibodies are efficacious in various malignancies.

Objectives: This study presents the first results of ipilimumab-nivolumab in invasive mucinous or non-mucinous lepidic adenocarcinoma (invasive mucinous adenocarcinoma (IMA) or invasive non-mucinous lepidic adenocarcinomas (INLA), respectively) of the lung.

Design: Dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) is a prospective, open-label, multicenter (1016 US sites), multi-cohort phase II trial of ipilimumab (1 mg/kg intravenously (IV) every 6 weeks) plus nivolumab (240 mg IV every 2 weeks).

Methods: Participants histologically diagnosed with advanced IMA or INLA, who had not responded to at least one line of therapy, were included in the bronchioloalveolar carcinoma cohort. The primary endpoint was the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (confirmed complete and partial responses (CR and PR)). Secondary endpoints were progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ⩾ 6 months plus ORR), and toxicity.

Results: Eight evaluable patients (median age: 77 years; the number of prior therapies ranged from 0 to 4; one patient with prior exposure to a PD-1 inhibitor; comprising six IMA and two INLA) were treated. One IMA had a 40% regression (PFS 45.2+ months, PD-L1 0%, KRAS G12C mutated, tumor mutational burden [TMB] 13 mut/Mb). One INLA had 66% regression (PFS 23.8 months, PD-L1 unknown, no actionable mutations, TMB 3 mut/Mb). Overall ORR was 25.0% (2/8) and CBR, 62.5% (5/8); PFS for the patients with SD > 6 months was 43.4+, 11.7+, and 8.3 months. The median PFS was 16 months (5.3-not reached) and the median OS was 32.2 months (14.6-not reached). The toxicity profile was similar to previous reports.

Conclusion: Ipilimumab plus nivolumab in the bronchioloalveolar carcinoma cohort (IMA, INLA) resulted in a durable ORR of 25.0% and CBR of 62.5% (PFS, 8.3 11.7+. 23.8 (PR), 43.4+ and 45.2+ (PR) months). Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies are warranted.

Trial registration: ClinicalTrials.gov registry: NCT02834013.

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来源期刊
CiteScore
8.20
自引率
2.00%
发文量
160
审稿时长
15 weeks
期刊介绍: Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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