Department of Oncology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Department of Medicine, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
J Clin Oncol. 2022 Sep 20;40(27):3180-3189. doi: 10.1200/JCO.21.02511. Epub 2022 Apr 27.
To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC).
Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits.
Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival.
Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.
评估纳武利尤单抗联合或不联合伊匹单抗联合立体定向体部放疗（SBRT）在难治性转移性胰腺癌（mPC）患者中的临床获益。
2016 年 11 月至 2019 年 12 月，根据体能状态将难治性 mPC 患者以 1:1 的比例随机分配接受 SBRT（15 Gy）联合纳武利尤单抗或纳武利尤单抗/伊匹单抗（ClinicalTrials.gov 标识符：NCT02866383）。主要终点为临床获益率（CBR），根据 RECIST 1.1 定义为完全或部分缓解（PR）或疾病稳定患者的百分比。Simon 的 2 阶段 2 期最佳设计分别用于 2 个臂，CBR 决定扩展到第 2 阶段。次要终点包括安全性、缓解率、缓解持续时间、无进展生存期和总生存期。探索性分析包括与获益相关的生物标志物。
84 例患者（41 例 SBRT/纳武利尤单抗和 43 例 SBRT/纳武利尤单抗/伊匹单抗）接受了至少一剂研究药物。SBRT/纳武利尤单抗组的 CBR 为 17.1%（8.0 至 30.6），SBRT/纳武利尤单抗/伊匹单抗组为 37.2%（24.0 至 52.1）。SBRT/纳武利尤单抗组中有 1 例患者出现 PR，持续时间为 4.6 个月。SBRT/纳武利尤单抗/伊匹单抗组中有 6 例患者出现 PR，缓解持续时间的中位数为 5.4 个月（4.2 至未达到）。SBRT/纳武利尤单抗组和 SBRT/纳武利尤单抗/伊匹单抗组中分别有 10 例（24.4%）和 13 例（30.2%）患者发生 3 级或更高级别的治疗相关不良事件。肿瘤比例评分≥1%的程序性死亡配体-1 表达或联合阳性评分≥1%与临床获益无关。治疗期间血清白细胞介素-6、白细胞介素-8 和 C 反应蛋白水平下降与总生存期改善相关。
在难治性 mPC 患者中，SBRT/纳武利尤单抗/伊匹单抗治疗后显示出有意义的抗肿瘤活性和良好的安全性。然而，SBRT 的作用尚不清楚。需要进一步的研究。
