Drug Development Unit, Sarah Cannon Research Institute UK, London, United Kingdom
Cancer Institute, University College London, London, United Kingdom.
Oncologist. 2018 Dec;23(12):1407-e136. doi: 10.1634/theoncologist.2018-0044. Epub 2018 May 31.
Ramucirumab plus pembrolizumab revealed no unexpected safety findings in patients with advanced or metastatic biliary tract cancer, which is consistent with reports of other tumor cohorts within this phase Ia/b trial.Ramucirumab plus pembrolizumab did not demonstrate an improvement in overall survival when compared with historical controls in biomarker unselected, heavily pretreated patients with advanced or metastatic biliary tract cancer.Patients with programmed death-ligand 1 (PD-L1)-positive tumors had improved overall survival compared with patients with PD-L1-negative disease.
Few treatment options exist for patients with advanced biliary tract cancer (BTC) following progression on gemcitabine-cisplatin. Preclinical evidence suggests that simultaneous blockade of vascular endothelial growth factor receptor 2 (VEGFR-2) and programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) enhances antitumor effects. We assessed the safety and efficacy of ramucirumab, an IgG1 VEGFR-2 antagonist, with pembrolizumab, an IgG4 PD-1 antagonist, in biomarker-unselected patients with previously treated advanced or metastatic BTC.
Patients had previously treated advanced or metastatic adenocarcinoma of the gallbladder, intrahepatic and extrahepatic bile ducts, or ampulla of Vater. Ramucirumab 8 mg/kg was administered intravenously on days 1 and 8 with intravenous pembrolizumab 200 mg on day 1 every 3 weeks. The primary endpoint was safety and tolerability of the combination. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Twenty-six patients were treated at 12 centers in five countries. Hypertension was the most common grade 3 treatment-related adverse event (TRAE), occurring in five patients. One patient experienced a grade 4 TRAE (neutropenia), and no treatment-related deaths occurred. Objective response rate was 4%. Median progression-free survival and overall survival were 1.6 months and 6.4 months, respectively.
Ramucirumabpembrolizumab showed limited clinical activity with infrequent grade 3-4 TRAEs in patients with biomarker-unselected progressive BTC.
拉鲁单抗联合派姆单抗用于晚期或转移性胆道癌患者，未发现新的安全性问题，与该 I 期/ Ib 试验中其他肿瘤队列的报告一致。拉鲁单抗联合派姆单抗与历史对照相比，在生物标志物未选择、晚期或转移性胆道癌患者中预处理的患者中，并未显示出总生存期的改善。程序性死亡配体 1（PD-L1）阳性肿瘤患者的总生存期优于 PD-L1 阴性疾病患者。
吉西他滨联合顺铂治疗进展后的晚期胆道癌（BTC）患者治疗选择有限。临床前证据表明，同时阻断血管内皮生长因子受体 2（VEGFR-2）和程序性死亡 1（PD-1）或程序性死亡配体 1（PD-L1）可增强抗肿瘤作用。我们评估了雷莫芦单抗（一种 IgG1VEGFR-2 拮抗剂）联合派姆单抗（一种 IgG4PD-1 拮抗剂）在未经生物标志物选择的晚期或转移性 BTC 患者中的安全性和疗效。
患者先前患有胆囊、肝内和肝外胆管或壶腹腺癌的晚期或转移性疾病。雷莫芦单抗 8mg/kg 静脉注射，第 1 天和第 8 天，第 1 天静脉注射派姆单抗 200mg，每 3 周一次。主要终点是联合用药的安全性和耐受性。次要终点包括客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
26 例患者在五个国家的 12 个中心接受治疗。高血压是最常见的 3 级治疗相关不良事件（TRAE），发生在 5 例患者中。1 例患者发生 4 级 TRAE（中性粒细胞减少症），无治疗相关死亡。客观缓解率为 4%。中位无进展生存期和总生存期分别为 1.6 个月和 6.4 个月。
雷莫芦单抗联合派姆单抗在未选择生物标志物的进展性 BTC 患者中显示出有限的临床活性，TRAE 发生率低且为 3-4 级。
