Supplementary Material for: Comparative Safety and Efficacy of Therapeutic Options in Resectable and Advanced/Metastatic Pancreatic Cancer: A Systematic Review and Indirect Comparison

Objectives: FOLFIRINOX, gemcitabine/nab-paclitaxel (gem-nab/P), and gemcitabine-capecitabine (gem-cap) demonstrated superiority over gemcitabine monotherapy for pancreatic cancer (PC). It is still unclear which chemotherapy regimen is the most optimal. This study aimed to conduct a systematic review (SR) and indirect comparison to compare safety and efficacy of FOLFIRINOX versus gem-nab/P and gem-cap in PC. Methods: An SR was conducted in several databases from inception to November 2020. RCTs investigating resectable or advanced PC were included. Primary outcomes including overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and grade 3/4 adverse events (AEs) were pooled using a random effects model. Indirect comparisons were done to compare FOLFIRINOX versus gem-cap and gem-nab/P. Heterogeneity was evaluated using Cochran’s Q test and I2 statistics. Results: Nine studies were identified involving 6,564 patients. Indirect comparisons showed FOLFIRINOX had significantly better OS (resectable: HR 0.78 [0.61–0.99]; advanced: HR 0.71 [0.60–0.85]) and RFS/DFS/PFS (resectable: HR 0.67 [0.55–0.82]; advanced: HR 0.65 [0.57–0.74]) compared to gem-cap as well as OS (resectable: HR 0.78 [0.61–1.00]; advanced: HR 0.73 [0.54–0.98]) and DFS/PFS (resectable: HR 0.66 [0.53–0.82]; advanced: HR 0.64 [0.49–0.83]) compared to gem-nab/P. FOLFIRINOX increased grade 3/4 AE risk compared to gem-cap and gem-nab/P. Conclusions: FOLFIRINOX is associated with significant survival benefits compared to gem-nab/P and gem-cap. However, it is important to consider the increased grade 3/4 AE risk associated with FOLFIRINOX.

研究目的：现有研究证实，FOLFIRINOX方案、吉西他滨/nab-紫杉醇（gemcitabine/nab-paclitaxel, gem-nab/P）以及吉西他滨/卡培他滨（gemcitabine-capecitabine, gem-cap）的治疗效果均优于吉西他滨单药治疗胰腺癌（pancreatic cancer, PC），但目前仍未明确哪种化疗方案为胰腺癌治疗的最优选择。本研究旨在开展系统评价（systematic review, SR）与间接比较分析，对比FOLFIRINOX方案与gem-nab/P、gem-cap方案治疗胰腺癌的安全性与有效性。
方法：本研究检索了多个医学数据库自建库至2020年11月的文献，纳入针对可切除或晚期胰腺癌的随机对照试验（randomized controlled trial, RCT）。采用随机效应模型合并分析主要结局指标，包括总生存期（overall survival, OS）、无病生存期（disease-free survival, DFS）/无进展生存期（progression-free survival, PFS）/无复发生存期（relapse-free survival, RFS）以及3/4级不良事件（adverse events, AEs）。通过间接比较分析对比FOLFIRINOX方案与gem-cap、gem-nab/P方案的疗效差异，采用Cochran Q检验及I²统计量评估研究间异质性。
结果：最终纳入9项研究，共计6564例患者。间接比较分析显示，相较于gem-cap方案，FOLFIRINOX方案可显著改善患者总生存期（可切除亚组：风险比HR=0.78，95%置信区间0.61~0.99；晚期亚组：HR=0.71，95%置信区间0.60~0.85）及无复发生存期/无病生存期/无进展生存期（可切除亚组：HR=0.67，95%置信区间0.55~0.82；晚期亚组：HR=0.65，95%置信区间0.57~0.74）；相较于gem-nab/P方案，FOLFIRINOX方案同样可显著改善总生存期（可切除亚组：HR=0.78，95%置信区间0.61~1.00；晚期亚组：HR=0.73，95%置信区间0.54~0.98）及无病生存期/无进展生存期（可切除亚组：HR=0.66，95%置信区间0.53~0.82；晚期亚组：HR=0.64，95%置信区间0.49~0.83）。相较于gem-cap与gem-nab/P方案，FOLFIRINOX方案会升高3/4级不良事件的发生风险。
结论：与gem-nab/P及gem-cap方案相比，FOLFIRINOX方案可带来显著的生存获益，但临床应用时需关注其伴随的3/4级不良事件风险升高的情况。