Department of Hematology/Oncology, Ronald Reagan UCLA Medical Center, Los Angeles, California.
Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Clin Cancer Res. 2020 Sep 15;26(18):4814-4822. doi: 10.1158/1078-0432.CCR-20-0099. Epub 2020 Jun 18.
Assess safety and efficacy of nivolumab plus -paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial.
Fifty chemotherapy-naive patients received -paclitaxel 125 mg/m plus gemcitabine 1,000 mg/m (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2). Secondary efficacy endpoints were progression-free survival (PFS), overall survival (OS), and response. Assessment of programmed cell death-ligand 1 (PD-L1) expression was an exploratory endpoint; additional biomarkers were assessed .
One DLT (hepatitis) was reported in part 1 among six DLT-evaluable patients; 48 of 50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median [95% confidence interval (CI)] PFS/OS was 5.5 (3.25-7.20 months)/9.9 (6.74-12.16 months) months, respectively [median follow-up for OS, 13.6 months (95% CI, 12.06-23.49 months)]. Overall response rate (95% CI) was 18% (8.6%-31.4%). Median PFS/OS was 5.5/9.7 months (PD-L1 <5%) and 6.8/11.6 months (PD-L1 ≥5%), respectively. Proportion of peripheral Ki67 CD8/CD4 cells increased significantly from baseline to cycle 3; median peak on-treatment Ki67 CD8 T-cell values were higher in responders than in nonresponders.
The safety profile of nivolumab plus -paclitaxel and gemcitabine at standard doses in advanced pancreatic cancer was manageable, with no unexpected safety signals. Overall, the clinical results of this study do not support further investigation.
在一项两部分、开放标签、I 期试验中，评估纳武利尤单抗联合紫杉醇和吉西他滨在局部晚期/转移性胰腺癌患者中的安全性和疗效。
50 名未经化疗的患者接受紫杉醇 125mg/m2 加吉西他滨 1000mg/m2（第 1、8 和 15 天）和纳武利尤单抗 3mg/kg（第 1 和 15 天），每 28 天为一个周期。主要终点是剂量限制毒性（DLT；第 1 部分）和 3/4 级治疗相关不良事件（TEAE）或因 TEAE 而停药（第 1/2 部分）。次要疗效终点是无进展生存期（PFS）、总生存期（OS）和反应。程序性死亡配体 1（PD-L1）表达评估是探索性终点；评估了其他生物标志物。
在 6 名可评估 DLT 的患者中，第 1 部分报告了 1 例 DLT（肝炎）；50 名患者中有 48 名发生 3/4 级 TEAEs，18 名因 TEAEs 停药。报告了 1 例 5 级不良事件（呼吸衰竭）。中位（95%置信区间[CI]）PFS/OS 分别为 5.5（3.25-7.20 个月）/9.9（6.74-12.16 个月）个月[OS 中位随访时间，13.6 个月（95%CI，12.06-23.49 个月）]。总缓解率（95%CI）为 18%（8.6%-31.4%）。中位 PFS/OS 分别为 5.5/9.7 个月（PD-L1<5%）和 6.8/11.6 个月（PD-L1≥5%）。从基线到第 3 周期，外周 Ki67 CD8/CD4 细胞比例显著增加；与无反应者相比，反应者的治疗中 Ki67 CD8 T 细胞的中位峰值更高。
纳武利尤单抗联合紫杉醇和吉西他滨在晚期胰腺癌中的标准剂量安全性可管理，无意外安全性信号。总体而言，这项研究的临床结果不支持进一步研究。
