Division of Hematology and Oncology, University of Cincinnati, Cincinnati, Ohio.
SWOG Statistical and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
JAMA Oncol. 2021 Mar 1;7(3):421-427. doi: 10.1001/jamaoncol.2020.7328.
Clinical outcomes after curative treatment of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. To assess the potential of early control of systemic disease with multiagent perioperative chemotherapy, we conducted a prospective trial.
To determine 2-year overall survival (OS) using perioperative chemotherapy for resectable PDA.
DESIGN, SETTING, AND PARTICIPANTS: This was a randomized phase 2 trial of perioperative chemotherapy with a pick-the-winner design. It was conducted across the National Clinical Trials Network, including academic and community centers all across the US. Eligibility required patients with Zubrod Performance Score of 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease per Intergroup criteria.
Perioperative (12 weeks preoperative, 12 weeks postoperative) chemotherapy with either fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX, arm 1) or gemcitabine/nab-paclitaxel (arm 2).
The primary outcome was 2-year overall survival (OS), using a pick-the-winner design; for 100 eligible patients, accrual up to 150 patients was planned to account for cases deemed ineligible at central radiology review.
From 2015 to 2018, 147 patients were enrolled; 43 patients (29%) had ineligible disease, beyond resectability criteria, at central radiology review. There were 102 eligible and evaluable patients, 55 in arm 1 and 47 in arm 2, of whom the median (range) age was 66 (44-76) and 64 (46-76) years, respectively; 36 patients (65%) in arm 1 and 24 (51%) in arm 2 were men. In arm 1, 34 (62%) had Zubrod Performance Score of 0, while in arm 2, 31 (66%) did; and 44 (80%) in arm 1 and 39 (83%) in arm 2 had head tumors. Of 102 patients, 84% and 85% completed preoperative chemotherapy, 73% and 70% underwent resection, and 49% and 40% completed all treatment. Adverse events were expected hematologic toxic effects, fatigue, and gastrointestinal toxicities. Two-year OS was 47% (95% CI, 31%-61%) for arm 1 and 48% (95% CI, 31%-63%) for arm 2; median OS was 23.2 months (95% CI, 17.6-45.9 months) and 23.6 months (95% CI, 17.8-31.7 months). Neither arm's 2-year OS estimate was significantly higher than the a priori threshold of 40%. Median disease-free survival after resection was 10.9 months in arm 1 and 14.2 months in arm 2.
This phase 2 randomized clinical trial did not demonstrate an improved OS with perioperative chemotherapy, compared with historical data from adjuvant trials in resectable pancreatic cancer. Two-year OS was 47% with mFOLFIRINOX and 48% with gemcitabine/nab-paclitaxel for all eligible patients starting treatment for resectable PDA. The trial also demonstrated adequate safety and high resectability rates with perioperative chemotherapy, and challenges in quality control for resectability criteria.
ClinicalTrials.gov Identifier: NCT02562716.
根治性治疗可切除胰腺导管腺癌（PDA）后的临床结果仍然不理想。为了评估多模式围手术期化疗早期控制系统性疾病的潜力，我们进行了一项前瞻性试验。
使用围手术期化疗评估可切除 PDA 的 2 年总生存率（OS）。
设计、地点和参与者：这是一项具有胜利者选择设计的围手术期化疗的随机 2 期试验。它在国家临床试验网络中进行，包括美国各地的学术和社区中心。符合条件的患者需要 Zubrod 表现评分 0 或 1、组织学证实的 PDA 诊断和根据 Intergroup 标准可切除疾病。
围手术期（术前 12 周，术后 12 周）化疗，使用氟尿嘧啶、伊立替康和奥沙利铂（mFOLFIRINOX，臂 1）或吉西他滨/纳布紫杉醇（臂 2）。
主要结局是 2 年 OS，使用胜利者选择设计；对于 100 名合格患者，计划招募 150 名患者，以弥补中心放射学审查认为不合格的病例。
2015 年至 2018 年，共纳入 147 名患者；43 名患者（29%）在中心放射学审查中发现超出可切除标准的疾病不可行。有 102 名合格且可评估的患者，55 名在臂 1，47 名在臂 2，其中中位（范围）年龄分别为 66（44-76）和 64（46-76）岁；36 名（65%）在臂 1 和 24 名（51%）在臂 2 为男性。在臂 1 中，34 名（62%）患者的 Zubrod 表现评分为 0，而在臂 2 中，31 名（66%）患者的评分为 0；44 名（80%）在臂 1 和 39 名（83%）在臂 2 有头肿瘤。在 102 名患者中，84%和 85%完成了术前化疗，73%和 70%接受了手术切除，49%和 40%完成了所有治疗。不良事件为预期的血液学毒性、疲劳和胃肠道毒性。臂 1 的 2 年 OS 为 47%（95%CI，31%-61%），臂 2 的 2 年 OS 为 48%（95%CI，31%-63%）；中位 OS 分别为 23.2 个月（95%CI，17.6-45.9 个月）和 23.6 个月（95%CI，17.8-31.7 个月）。两个臂的 2 年 OS 估计均未显著高于事先设定的 40%的阈值。在接受手术切除的患者中，臂 1 的中位无病生存期为 10.9 个月，臂 2 为 14.2 个月。
与可切除胰腺癌辅助试验的历史数据相比，这项 2 期随机临床试验并未显示围手术期化疗可改善 OS。所有开始接受可切除 PDA 治疗的合格患者中，mFOLFIRINOX 的 2 年 OS 为 47%，吉西他滨/纳布紫杉醇为 48%。该试验还证明了围手术期化疗具有足够的安全性和较高的可切除率，以及在可切除性标准的质量控制方面存在挑战。
ClinicalTrials.gov 标识符：NCT02562716。
