局部晚期胰腺癌患者的立体定向放疗加 Nivolumab：CA209-9KH 1/2期临床试验结果。

IF 3.2 Q2 ONCOLOGY Oncology and Therapy Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI:10.1007/s40487-024-00309-z

Milan Vošmik, Stanislav John, Josef Dvořák, Beatrice Mohelníková-Duchoňová, Bohuslav Melichar, Radka Lohynská, Aleš Ryška, Aml Mustafa Banni, Johana Krempová, Igor Sirák

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引用次数: 0

摘要

简介：胰腺导管腺癌（PDAC）的预后不佳凸显了对新型治疗策略的迫切需求。在大多数 PDAC 研究中，免疫检查点抑制剂（ICIs）似乎效果不佳。因此，我们开展了一项开放标签、多中心1/2期研究（CA209-9KH），以评估立体定向放射治疗（SRT）和序贯ICI治疗在PDAC中的安全性，并验证该方案作为抗肿瘤免疫潜在激活剂的疗效：方法：纳入年龄≥ 18 岁、经过四个 FOLFIRINOX 诱导周期治疗后仍无法切除的非转移性 PDAC 患者。治疗包括 SRT（4 × 8 Gy）和连续使用 nivolumab，直至疾病进展或出现不可接受的毒性。主要终点是安全性和毒性评估。次要终点包括无进展生存期（PFS）、总生存期（OS）、生物标志物评估和生活质量（QoL）分析：共筛选出 22 例患者，其中 15 例入组。共进行了 11 个 nivolumab 周期（中位数）的治疗。SRT显示出较低且无临床意义的毒性，而nivolumab的毒性与之前的安全性概况一致，未观察到4-5级事件。三名患者因毒性而中断治疗。中位 PFS 和 OS 分别为 8.1 个月和 13.0 个月，12 个月的 PFS 和 OS 率分别为 0% 和 66.7%，24 个月的 OS 率为 8.9%。生物标志物水平与临床或放射学疾病控制相关。患者报告的生活质量仍可接受，但随疾病进展而恶化：SRT和nivolumab疗法表现出可控的毒性，这与之前的研究结果一致；然而，在局部晚期PDAC患者中，该疗法并未取得长期治疗效果。需要寻找另一种策略来触发PDAC的抗肿瘤免疫：试验注册：EudraCT：2017-003404-52；ClinicalTrials.gov：NCT04098432。

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Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial.

Introduction: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity.

Methods: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis.

Results: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression.

Conclusion: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought.

Trial registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

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来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. 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