Lessons learned: 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.
Background: 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.
Methods: 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).
Results: 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.
Conclusion: Ramucirumab-pembrolizumab showed limited clinical activity with infrequent grade 3-4 TRAEs in patients with biomarker-unselected progressive BTC.
摘要
背景。 吉西他滨‐顺铂治疗出现进展后,几乎没有治疗方案可以治疗晚期胆管癌 (BTC) 患者。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。我们在经治的晚期或转移性 BTC、生物标志物未经选患者中评估了 IgG1 VEGFR‐2 拮抗剂雷莫芦单抗和 IgG4 PD‐1 拮抗剂派姆单抗的安全性和有效性。
方法. 患者为经治的晚期或转移性胆囊腺癌、肝内外胆管或 Vater 壶腹癌。分别于第1天和第8天静脉注射雷莫芦单抗8mg/kg,第1天静脉注射派姆单抗200mg,每3周一次。主要终点是联合给药的安全性和耐受性。次要终点包括客观有效率 (ORR)、无进展生存期 (PFS) 和总生存期 (OS)。
结果。26例患者在5个国家的12个中心进行了治疗。高血压是最常见的3级治疗相关不良事件 (TRAE),在5例患者中发生。1例患者出现了4级 TRAE(中性粒细胞减少症),未发生治疗相关死亡病例。客观有效率为4%。中位无进展生存期和总生存期分别为1.6和6.4个月。
结论。 在生物标志物未经选的进展性 BTC 患者中,雷莫芦单抗联合派姆单抗显示出有限的临床活性,3‐4级 TRAE 不常见
Trial registration: ClinicalTrials.gov NCT02443324.
© AlphaMed Press; the data published online to support this summary are the property of the authors.