Mastrantoni Luca, Chiaravalli Marta, Spring Alexia, Beccia Viria, Di Bello Armando, Bagalà Cinzia, Bensi Maria, Barone Diletta, Trovato Giovanni, Caira Giulia, Giordano Giulia, Bria Emilio, Tortora Giampaolo, Salvatore Lisa
Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy.
Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy.
Lancet Oncol. 2024 Dec;25(12):1655-1665. doi: 10.1016/S1470-2045(24)00511-4. Epub 2024 Nov 11.
BACKGROUND: In advanced pancreatic ductal adenocarcinoma (PDAC), first-line chemotherapy is the standard of care. Due to the absence of head-to-head comparisons in clinical trials, we performed this systematic review and network meta-analysis to compare treatment options for PDAC in terms of their efficacy and toxicity. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase, and oncological meetings websites were searched until Nov 15, 2023. We included phase 2-3 randomised controlled trials published after Jan 1, 2000, evaluating first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC. Primary endpoints assessed were progression-free survival and overall survival. Summary data were extracted from published reports. The deviance information criterion was used to choose between a random-effects or fixed-effects model. Hazard ratios (HRs) with 95% credible intervals were estimated using a Bayesian approach. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool and studies were graded as low, some concerns, or high risk of bias. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. This systematic review and network meta-analysis is registered with PROSPERO, CRD42023450330. FINDINGS: 6050 records were screened and 79 randomised controlled trials (22 168 patients) were included in the analysis. Gemcitabine was the most frequent comparator (in 50 [63%] of 79 trials) and was considered as the reference treatment. A fixed-effect model was used to analyse the primary outcomes. Regarding progression-free survival (71 trials, 19 479 patients), the most effective treatments were gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0·32, 95% credible interval 0·22-0·47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0·35, 0·22-0·55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0·43, 0·34-0·54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0·55, 0·47-0·65) and gemcitabine plus nab-paclitaxel (0·62, 0·54-0·72). Similar results were observed for overall survival (79 trials, 22 104 patients): PAXG (HR 0·40, 95% credible interval 0·25-0·65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0·46, 0·32-0·66), and NALIRIFOX (0·56, 0·45-0·70) had the highest benefit, followed by FOLFIRINOX (0·66, 0·56-0·78) and gemcitabine plus nab-paclitaxel (0·67, 0·59-0·77). The overall risk of bias was low to some concerns. Certainty of evidence was low. INTERPRETATION: Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 randomised controlled trials investigating concomitant or sequential quadruplets are warranted. FUNDING: None.
背景：在晚期胰腺导管腺癌（PDAC）中，一线化疗是标准治疗方案。由于临床试验中缺乏直接对比，我们进行了这项系统评价和网状Meta分析，以比较PDAC的各种治疗方案在疗效和毒性方面的差异。 方法：检索了PubMed、Cochrane对照试验中央注册库、Embase以及肿瘤学会议网站，检索截至2023年11月15日。我们纳入了2000年1月1日后发表的2-3期随机对照试验，这些试验评估了先前未治疗、不可切除、局部晚期或转移性PDAC患者的一线治疗。评估的主要终点为无进展生存期和总生存期。从已发表的报告中提取汇总数据。采用偏差信息准则在随机效应模型或固定效应模型之间进行选择。使用贝叶斯方法估计具有95%可信区间的风险比（HR）。使用Cochrane偏倚风险2（RoB 2）工具评估偏倚风险，研究被分为低、有些担忧或高偏倚风险等级。使用推荐分级评估、制定和评价方法评估证据质量。本系统评价和网状Meta分析已在PROSPERO注册，注册号为CRD42023450330。 结果：共筛选了6050条记录，79项随机对照试验（22168例患者）纳入分析。吉西他滨是最常见的对照药物（79项试验中的50项[63%]），并被视为对照治疗。采用固定效应模型分析主要结局。关于无进展生存期（71项试验，19479例患者），最有效的治疗方案是吉西他滨联合白蛋白结合型紫杉醇交替使用亚叶酸钙、氟尿嘧啶和奥沙利铂（[FOLFOX]，HR 0.32，95%可信区间0.22-0.47）、顺铂、白蛋白结合型紫杉醇、卡培他滨和吉西他滨（[PAXG]，0.35，0.22-0.55）以及脂质体伊立替康联合氟尿嘧啶、亚叶酸钙和奥沙利铂（[NALIRIFOX]，0.43，0.34-0.54），其次是氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂（[FOLFIRINOX]，0.55，0.47-0.65）以及吉西他滨联合白蛋白结合型紫杉醇（0.62，0.54-0.72）。总生存期（79项试验，22104例患者）的结果相似：PAXG（HR 0.40，95%可信区间0.25-0.65）、吉西他滨联合白蛋白结合型紫杉醇交替使用FOLFOX（0.46，0.32-0.66）和NALIRIFOX（0.56，0.45-0.70）获益最高，其次是FOLFIRINOX（0.66，0.56-0.78）和吉西他滨联合白蛋白结合型紫杉醇（0.67，0.59-0.77）。总体偏倚风险为低到有些担忧。证据确定性低。 解读：我们的研究结果表明，对于能够耐受这些方案的患者，NALIRIFOX和FOLFIRINOX应作为首选方案，吉西他滨联合白蛋白结合型紫杉醇仍是一种可行的替代方案，特别是对于不适合三联疗法的患者。有必要开展3期随机对照试验来研究同步或序贯四联疗法。 资金来源：无。
Cochrane Database Syst Rev. 2018-4-6
Cochrane Database Syst Rev. 2018-3-20
Cochrane Database Syst Rev. 2018-2-6
Cochrane Database Syst Rev. 2017-8-29
Cochrane Database Syst Rev. 2021-4-19
J Gastrointest Oncol. 2025-6-30
Zotero 插件