The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527;p= 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764;p= 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals.
本研究评估了奥拉单抗联合白蛋白结合型紫杉醇和吉西他滨治疗初治转移性胰腺导管腺癌患者的疗效与安全性。研究首先开展了一项1b期剂量递增试验，以确定后续2期试验中奥拉单抗的给药剂量。2期试验为随机、双盲、安慰剂对照研究，旨在比较奥拉单抗组与安慰剂组的总生存期。在1b期试验中，22名受试者接受了15 mg/kg和20 mg/kg剂量的奥拉单抗联合固定剂量的白蛋白结合型紫杉醇和吉西他滨治疗。在2期试验中，159名受试者被随机分配至奥拉单抗组（n=81）或安慰剂组（n=78），两组均联合使用白蛋白结合型紫杉醇和吉西他滨。奥拉单抗组在第1个治疗周期接受20 mg/kg剂量，后续周期调整为15 mg/kg剂量，给药方案为28天周期的第1、8、15天。研究主要终点未达到，奥拉单抗组与安慰剂组的中位总生存期分别为9.1个月与10.8个月（风险比=1.05；95%置信区间：0.728-1.527；p=0.79），中位无进展生存期分别为5.5个月与6.4个月（风险比=1.19；95%置信区间：0.806-1.764；p=0.38）。两组中最常见的各级别治疗期间不良事件均为疲劳。奥拉单抗联合化疗未能改善转移性胰腺导管腺癌患者的总生存期或无进展生存期，未发现新的安全性信号。
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