The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma.
The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma.
复制标题
DOI：
10.1038/s41467-022-32591-8
复制
发表时间：
2022-08-26
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
转移性胰腺导管腺癌（mPDAC）中基于免疫疗法的单药治疗在错配修复缺陷背景之外显示出有限的益处，而双检查点抑制剂免疫疗法与化疗联合的安全性和疗效仍不确定。在这里，我们介绍了CCTG PA.7研究（NCT 02879318）的结果，这是一项随机II期试验，在180例mPDAC患者中比较了吉西他滨和nab-紫杉醇联合和不联合免疫检查点抑制剂durvalumab和tremelimumab。主要终点是总生存期。次要终点包括无进展生存期和客观缓解率。试验结果是阴性的，因为联合免疫治疗没有改善COPD患者群体的生存率（p = 0.72），并且毒性仅限于联合免疫治疗组中淋巴细胞的升高（p = 0.02）。探索性基线循环肿瘤DNA（ctDNA）测序显示，在联合免疫治疗（p = 0.001）和化疗（p = 0.004）组中，KRAS野生型肿瘤患者的生存率增加。这些数据支持ctDNA分析在PDAC中的实用性和基于ctDNA的KRAS突变状态的预后价值。转移性胰腺导管腺癌（mPDAC）的治疗选择有限，且预后不良。在本文中，作者报告了一项随机II期试验的结果，该试验显示，与mPDAC患者单独化疗相比，检查点抑制剂（durvalumab和tremelimumab）与化疗（吉西他滨和nab-紫杉醇）联合使用并不能改善生存率。
Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status. Metastatic pancreatic ductal adenocarcinoma (mPDAC) has limited therapeutic options and is associated with a poor prognosis. Here the authors report the results of a randomized phase II trial showing that combining checkpoint inhibitors (durvalumab and tremelimumab) with chemotherapy (gemcitabine and nab-paclitaxel) does not improve survival compared to chemotherapy alone in patients with mPDAC.
登录
查看更多内容
杜瓦卢马布（Durvalumab）和非小细胞肺癌中的tremelimumab的安全性和抗肿瘤活性：多中心1B研究。
DOI：
10.1016/s1470-2045(15)00544-6
发表时间：
2016-03
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Antonia S;Goldberg SB;Balmanoukian A;Chaft JE;Sanborn RE;Gupta A;Narwal R;Steele K;Gu Y;Karakunnel JJ;Rizvi NA
通讯作者：
Rizvi NA
影响因子：
8.3
作者：
Porta M;Pumarega J;Amaral AFS;Genkinger JM;Camargo J;Mucci L;Alguacil J;Gasull M;Zhang X;Morales E;Iglesias M;Ogino S;Engel LS;PANKRAS II Study Group
通讯作者：
PANKRAS II Study Group
影响因子：
45.3
作者：
O'Reilly, Eileen M.;Lee, Jonathan W.;Kelsen, David P.
通讯作者：
Kelsen, David P.
影响因子：
11.5
作者：
Jones, Martin R.;Williamson, Laura M.;Renouf, Daniel J.
通讯作者：
Renouf, Daniel J.
定量多重免疫组织化学揭示了与不良预后相关的骨髓炎症肿瘤免疫复杂性。
影响因子：
8.8
作者：
Tsujikawa T;Kumar S;Borkar RN;Azimi V;Thibault G;Chang YH;Balter A;Kawashima R;Choe G;Sauer D;El Rassi E;Clayburgh DR;Kulesz-Martin MF;Lutz ER;Zheng L;Jaffee EM;Leyshock P;Margolin AA;Mori M;Gray JW;Flint PW;Coussens LM
通讯作者：
Coussens LM