Importance Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations, indicating a DNA repair deficiency associated with sensitivity to DNA damaging agents, such as platinum.

Objective To determine response rate following treatment with nab-paclitaxel plus gemcitabine plus platinum-based cisplatin for patients with metastatic pancreatic ductal adenocarcinoma (PDA).

Design, Setting, and Participants This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus cisplatin treatment in which 25 patients with previously untreated metastatic PDA were enrolled. The trial was conducted from December 2013 to July 2016 at 3 US sites, with the last patient receiving study treatment at the end of October 2016, and the study closing January 2018.

Interventions Patients were treated with nab-paclitaxel plus gemcitabine plus various doses of cisplatin, 25 mg/m², 37.5 mg/m², and 50 mg/m², on days 1 and 8 of a 21-day cycle.

Main Outcomes and Measures Primary end point was complete response rate as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and levels of carbohydrate antigen 19-9 (or in nonexpressers, carbohydrate antigen 125 or carcinoembryonic antigen). Efficacy analysis included evaluable patients (those who received at least 1 dose of study treatment and had at least 1 postbaseline tumor assessment).

Results Of 25 patients enrolled in the study, the median (range) age was 65.0 (47.0-79.0) years, 14 (56%) were men, and most (24) were white (96%). The maximum tolerable dose of cisplatin was 25 mg/m². The most common treatment-related adverse events grade 3 or higher were thrombocytopenia (17 patients [68%]), anemia (8 patients [32%]), and neutropenia (6 patients [24%]). Fatal events occurred for 3 patients (12%); 2 were related to study participation. A median (range) of 8 (1-15) cycles was completed. The RECIST responses in 24 evaluable patients included 2 complete responses (8%), which was below the primary end point of 25%, 15 partial responses (62%), 4 stable disease (17%), and 3 progressive disease (12%), with median overall survival of 16.4 (95% CI, 10.2-25.3) months; 16 patients (64%) were alive at 1 year, 10 (40%) at 2 years, 4 (16%) at 3 years, and 1 (4%) at 4 plus years. Overall survival ranged from 36 to 59 months. Median progression-free survival was 10.1 (95% CI, 6.0-12.5) months. Thus, the overall response rate was 71%, and the disease control rate was 88%.

Conclusions and Relevance This triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging. The regimen is being studied in patients with PDA in the neoadjuvant setting and in patients with advanced biliary cancers.

Trial Registration ClinicalTrials.gov identifier: NCT01893801

重要性 转移性胰腺癌的基因组经常包含染色体内畸变，表明 DNA 修复缺陷与对 DNA 损伤剂（如铂）的敏感性相关。

目的 确定白蛋白结合型紫杉醇联合吉西他滨联合铂类顺铂治疗转移性胰腺导管腺癌（PDA）患者的反应率。

设计、设置和参与者 这是一项单臂、开放标签、1b/2 期白蛋白结合型紫杉醇加吉西他滨加顺铂治疗的临床试验，纳入了 25 名先前未经治疗的转移性 PDA 患者。该试验于 2013 年 12 月至 2016 年 7 月在美国 3 个地点进行，最后一名患者于 2016 年 10 月末接受研究治疗，研究于 2018 年 1 月结束。

干预 患者在21 天周期的第 1 天和第 8 天接受白蛋白结合型紫杉醇加吉西他滨加各种剂量的顺铂（25 mg/m ²、37.5 mg/m ²和 50 mg/m ^{2 ）治疗。}

主要结果和措施 主要终点是通过实体瘤反应评估标准 1.1 版 (RECIST) 评估的完全反应率，以及碳水化合物抗原 19-9（或在非表达者中，碳水化合物抗原 125 或癌胚抗原）的水平。疗效分析包括可评估的患者（接受了至少 1 剂研究治疗并进行了至少 1 次基线后肿瘤评估的患者）。

结果 参加研究的 25 名患者中位（范围）年龄为 65.0（47.0-79.0）岁，14 名（56%）为男性，大多数（24 名）为白人（96%）。顺铂的最大耐受剂量为 25 mg/m ². 最常见的 3 级或更高级别的治疗相关不良事件是血小板减少症（17 例患者 [68%]）、贫血症（8 例患者 [32%]）和中性粒细胞减少症（6 例患者 [24%]）。3 名患者 (12%) 发生了致命事件；2个与研究参与有关。完成了 8 (1-15) 个周期的中位数（范围）。24 名可评估患者的 RECIST 反应包括 2 名完全反应（8%），低于主要终点 25%、15 名部分反应（62%）、4 名疾病稳定（17%）和 3 名疾病进展（12%） )，中位总生存期为 16.4 (95% CI, 10.2-25.3) 个月；16 名患者 (64%) 在 1 年存活，10 名 (40%) 在 2 年存活，4 名 (16%) 在 3 年存活，1 名 (4%) 在 4 年以上存活。总生存期为 36 至 59 个月。中位无进展生存期为 10.1 (95% CI, 6.0-12.5) 个月。因此，总体响应率为 71%，

结论和相关性 这种三联药物方案在这项小型研究中显示出显着的临床活性。尽管未达到主要终点，但在接受这种联合治疗的晚期 PDA 患者中，高总缓解率、疾病控制率和中位生存时间令人鼓舞。该方案正在新辅助治疗中的 PDA 患者和晚期胆管癌患者中进行研究。

试验注册 ClinicalTrials.gov 标识符：NCT01893801