Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.
Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.
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卡瑞利珠单抗联合吉西他滨和奥沙利铂 (GEMOX) 治疗晚期胆道癌患者：一项单臂、开放标签 II 期试验
DOI：
10.1136/jitc-2020-001240
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发表时间：
2020-11
影响因子：
10.9
通讯作者：
Shu Y
中科院分区：
文献类型：
--
作者：
Chen X;Wu X;Wu H;Gu Y;Shao Y;Shao Q;Zhu F;Li X;Qian X;Hu J;Zhao F;Mao W;Sun J;Wang J;Han G;Li C;Xia Y;Seesaha PK;Zhu D;Li H;Zhang J;Wang G;Wang X;Li X;Shu Y
已在晚期胆道癌（BTC）患者中研究了免疫检查点抑制剂单药治疗。本研究的目的是评估camrelizumab+吉西他滨和奥沙利铂（GEMOX）作为一线治疗晚期BTC的疗效和安全性，并探索与缓解相关的潜在生物标志物。在这项单组、开放标签、II期研究中，我们招募了IV期BTC患者。参与者接受camrelizumab（3 mg/kg）+吉西他滨（800 mg/m2）和奥沙利铂（85 mg/m2）。主要终点是6个月无进展生存期（PFS）率和安全性。次要终点为客观缓解率（ORR）、PFS和总生存期（OS）。探索性终点包括缓解与肿瘤突变负荷（TMB）、血液TMB、ctDNA动态变化和免疫微环境之间的相关性。筛选了54例晚期BTC患者，其中38例合格患者入组。1例患者在首次给药治疗前撤回知情同意书。中位随访时间为11.8个月。6个月PFS率为50%（95% CI 33 - 65）。37例患者中有20例（54%）出现客观缓解。中位PFS为6.1个月，中位OS为11.8个月。最常见的治疗相关不良事件（TRAE）为疲乏（27例（73%））和发热（27例（73%））。最常见的3级或更严重TRAE为低钾血症（7例（19%））和疲乏（6例（16%））。程序性细胞死亡配体-1（PD-L1）肿瘤比例评分（TPS）≥1%的患者的ORR为80%，而PD-L1 TPS <1%的患者为53.8%。除PFS与血TMB相关外，TMB、血TMB、免疫比例评分和免疫细胞数与疗效无关（p>0.05）。治疗后ctDNA阳性的患者的PFS较短（p=0.007; HR，2.83; 95%CI 1.27至6.28）。Camrelizumab + GEMOX作为晚期BTC患者的一线治疗显示出有希望的抗肿瘤活性和可接受的安全性特征。需要潜在的生物标志物来识别可能对camrelizumab + GEMOX有反应的患者。NCT 03486678。
Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response. In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment. 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28). Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX. NCT03486678.
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影响因子：
45.3
作者：
Heymach, John;Krilov, Lada;Burstein, Harold
通讯作者：
Burstein, Harold
影响因子：
8.8
作者：
Andre, T.;Reyes-Vidal, J. M.;Fartoux, L.;Ross, P.;Leslie, M.;Rosmorduc, O.;Clemens, M. R.;Louvet, C.;Perez, N.;Mehmud, F.;Scheithauer, W.
通讯作者：
Scheithauer, W.
DOI：
10.1158/1078-0432.ccr-17-1341
发表时间：
2018-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Goldberg SB;Narayan A;Kole AJ;Decker RH;Teysir J;Carriero NJ;Lee A;Nemati R;Nath SK;Mane SM;Deng Y;Sukumar N;Zelterman D;Boffa DJ;Politi K;Gettinger SN;Wilson LD;Herbst RS;Patel AA
通讯作者：
Patel AA
影响因子：
50.5
作者：
Lee, J. H.;Long, G. V.;Rizos, H.
通讯作者：
Rizos, H.
影响因子：
3
作者：
Jang, Joung-Soon;Lim, Ho Yeong;Lee, Sang Jae
通讯作者：
Lee, Sang Jae