Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study
Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study
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DOI：
10.1016/s2468-1253(19)30327-9
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发表时间：
2020-03-01
影响因子：
35.7
通讯作者：
Hammel, Pascal
中科院分区：
文献类型：
--
作者：
Philip, Philip A.;Lacy, Jill;Hammel, Pascal
不能切除的局部晚期胰腺癌患者的治疗选择很少。转移性胰腺癌3期MPACT试验的亚组分析结果表明，nab-紫杉醇联合吉西他滨对局部晚期胰腺癌具有潜在活性。这2期试验的目的是评估安全性和疗效的nab-紫杉醇加吉西他滨在以前未经治疗的局部晚期pancreat.Methods的国际，开放标签，多中心，2期试验（LAPACT）发生在35个网站在5个国家（美国，法国，西班牙，加拿大和意大利）。东部肿瘤协作组体力状态评分最高为1分的患者接受6个周期的白蛋白结合型紫杉醇125 mg/m2+吉西他滨1000 mg/m2诱导治疗（每个28天周期的第1、8和15天）。诱导后，没有进展性疾病或不可接受的不良事件的患者有资格接受研究者选择的继续治疗：继续nab-紫杉醇加吉西他滨、放化疗或手术。主要终点是至治疗失败的时间;次要终点是疾病控制率、总缓解率、无进展生存期、总生存期、安全性和生活质量。在意向治疗人群中分析了报告的疗效结局，在治疗人群中分析了安全性结局。该试验已在ClinicalTrials.gov、NCT 02301143和EudraCT 2014-001408-23上注册，并已完成。106例患者接受了研究治疗; 1例患者入组但未接受治疗。107名入组患者中有44名（41%）停止诱导;停止诱导的最常见原因是不良事件（22 121%1例患者）。107例入组患者中的62例（58%）完成诱导治疗，47例（44%）患者随后根据研究者的选择接受继续治疗：12例（11%）继续nab-紫杉醇加吉西他滨，18例（17%）接受放化疗，17例（16%）接受手术（7例为RO切除状态，9例为R1）。15例（14%）患者完成了诱导治疗，但未接受继续治疗。至治疗失败的中位时间为9. 0个月（90% CI 7. 3 -10-1）;中位无进展生存期为10. 9个月（90% CI 9. 3 - 11. 6），中位总生存期为18. 8个月（90% CI 15 - 0-24 - 0）。在诱导期间，83例患者达到疾病控制，疾病控制率为77.6%（90%CI 70.3-83.5）。36例患者的最佳缓解为部分缓解;诱导期间的总缓解率为33.6%（90% CI 26-6-41.5）。诱导期治疗人群中最常见的3级或以上治疗后出现的不良事件为中性粒细胞减少（35/106例患者[33%]）、贫血（12 MN）和疲乏（11 [10%]）。诱导期间最常见的治疗后出现的严重不良事件为肺炎（5例[5%]患者）、发热（5例[5%]）和发热性中性粒细胞减少症（3例[3%]）。在诱导阶段，没有死亡是由治疗相关的不良事件引起的，在大多数patients.Interpretation的全球生活质量得到维持。该试验的数据支持nab-紫杉醇加吉西他滨治疗局部晚期胰腺癌的耐受性和活性，以及将不可切除的局部晚期疾病转化为可手术切除的疾病的潜力。安全性特征与既往结果基本一致。版权所有（C）2020爱思唯尔有限公司保留所有权利。
Background Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the phase 3 MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this phase 2 trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer.Methods This international, open-label, multicentre, phase 2 trial (LAPACT) took place at 35 sites in five countries (USA, France, Spain, Canada, and Italy). Patients with Eastern Cooperative Oncology Group performance status of up to 1 underwent six cycles of induction with nab-paclitaxel 125 mg/m(2) plus gemcitabine 1000 mg/m(2) (days 1,8, and 15 of each 28-day cycle). After induction, patients without progressive disease or unacceptable adverse events were eligible to receive continued therapy per investigator's choice: continued nab-paclitaxel plus gemcitabine, chemoradiation, or surgery. The primary endpoint was time to treatment failure; secondary endpoints were disease control rate, overall response rate, progression-free survival, overall survival, safety, and quality of life. The reported efficacy outcomes were analysed in the intention-to-treat population, and safety outcomes were analysed in the treated population. This trial is registered with ClinicalTrials.gov, NCT02301143, and EudraCT, 2014-001408-23 and is complete.Findings Between April 21,2015, and April 26, 2018, 107 patients were enrolled in the study. 106 received the study treatment; one patient enrolled but did not receive treatment. 44 (41%) of 107 enrolled patients discontinued induction; the most common reason for discontinuing induction was adverse events (22 121%1 patients). 62 (58%) of 107 enrolled patients completed induction treatment and 47 (44%) patients subsequently received continued treatment per investigator's choice: 12 (11%) continued nab-paclitaxel plus gemcitabine, 18 (17%) received chemoradiation, and 17 (16%) underwent surgery (seven had RO resection status, nine had R1). 15 (14%) patients completed induction treatment but did riot receive continued treatment. Median time to treatment failure was 9.0 months (90% CI 7.3-10-1); median progression-free survival was 10.9 months (90% CI 9.3-11.6), and median overall survival was 18.8 months (90% CI 15 - 0-24 - 0). During induction, 83 patients achieved disease control and the disease control rate was 77.6% (90% CI 70.3-83.5). 36 patients had a best response of partial response; the overall response rate during induction was 33.6% (90% CI 26-6-41.5). The most common treatment-emergent adverse events that were grade 3 or higher in the treated population during induction were neutropenia (35 [33%] of 106 patients), anaemia (12 MN), and fatigue (11 [10%]). The most cormnon treatment-emergent serious adverse events during induction were pneumonia (five [5%] patients), pyrexia (five [5%]), and febrile neutropenia (three [3%]). No deaths were caused by treatment-related adverse events during the induction phase, and global quality of life was maintained in most patients.Interpretation The data from this trial support the tolerability and activity of nab-paclitaxel plus gemcitabine for locally advanced pancreatic cancer, and a potential to convert unresectable, locally advanced disease to surgically resectable disease. The safety profile was generally consistent with previous findings. Copyright (C) 2020 Elsevier Ltd. All rights reserved.