PDF(Pubmed)
Abstract：
UNASSIGNED: The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
UNASSIGNED: To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
UNASSIGNED: After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings\' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
UNASSIGNED: Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
UNASSIGNED: Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
UNASSIGNED: The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
UNASSIGNED: A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
UNASSIGNED: In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
UNASSIGNED: To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
UNASSIGNED: After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings\' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
UNASSIGNED: Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
UNASSIGNED: Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
UNASSIGNED: The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
UNASSIGNED: A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
UNASSIGNED: In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
摘要：
■NAPOLI3试验显示了氟尿嘧啶的优越性，亚叶酸,脂质体伊立替康,和奥沙利铂（NALIRIFOX）相对于吉西他滨和nab-紫杉醇（GEM-NABP）的组合作为转移性胰腺导管腺癌（PDAC）的一线治疗。NALIRIFOX和GEM-NABP与氟尿嘧啶的比较分析，亚叶酸,伊立替康,和奥沙利铂（FOLFIRINOX）尚未报告。
■为了获得生存，回应,和来自3期临床试验的毒性效应数据，并比较NALIRIFOX，FOLFIRINOX,和GEM-NABP。
■经过对PubMed的系统搜索，Scopus,Embase,和美国临床肿瘤学会和欧洲医学肿瘤学会图书馆会议，从2011年1月1日至2023年9月12日进行的3期临床试验中提取Kaplan-Meier曲线。
■测试NALIRIFOX的3期临床试验，FOLFIRINOX,选择GEM-NABP或GEM-NABP作为转移性PDAC的一线治疗,并选择报告的总生存期(OS)和无进展生存期(PFS)曲线.本研究遵循了个人参与者数据报告指南的系统审查和荟萃分析的首选报告项目。
■通过图形重建算法从原始试验的Kaplan-Meier图中提取个体患者OS和PFS数据。还收集了总反应率（ORR）和3级或更高的毒性作用率。进行了汇总分析，结果通过网络荟萃分析进行验证.
■主要终点是OS。次要结果包括PFS，ORR,和毒性效应率。
■共分析了2581名患者的7项试验数据，包括383名接受NALIRIFOX治疗的患者，433例接受FOLFIRINOX治疗的患者，1756例患者接受GEM-NABP治疗。接受NALIRIFOX（7.4[95%CI，6.1-7.7]个月）或FOLFIRINOX（7.3[95%CI，6.5-7.9]个月；[HR]，1.21[95%CI，0.86-1.70]；P=.28）与GEM-NABP治疗的患者相比（5.7[95%CI，5.6-6.1]个月；HR与NALIIFOX，1.45[95%CI，1.22-1.73]；P<.001）。同样，GEM-NABP与NALIRIFOX（HR，1.18[95%CI，1.00-1.39]；P=0.05]，而FOLFIRINOX(11.7[95%CI,10.4-13.0]个月)和NALIIFOX(11.1[95%CI,10.1-12.3]个月;HR,1.06[95%CI，0.81-1.39]；P=.65）。NALIIFOX之间的ORR差异无统计学意义（41.8％），FOLFIRINOX（31.6％），和创业板-NABP（35.0%）。NALIRIFOX与较低的3级或更高的血液学毒性作用发生率相关（例如，血小板计数下降1.6%vsFOLFIRINOX的11.8%和GEM-NABP的10.8%)，但与GEM-NABP相比，严重腹泻的发生率更高（20.3％vs15.7％）。
■在本系统综述和荟萃分析中，NALIRIFOX和FOLFIRINOX与一线治疗晚期PDAC的PFS和OS相似，尽管NALIRIFOX与不同的毒性特征相关。精心挑选病人,金融毒性影响的考虑，FOLFIRINOX和NALIIFOX之间的直接比较是必要的。
■为了获得生存，回应,和来自3期临床试验的毒性效应数据，并比较NALIRIFOX，FOLFIRINOX,和GEM-NABP。
■经过对PubMed的系统搜索，Scopus,Embase,和美国临床肿瘤学会和欧洲医学肿瘤学会图书馆会议，从2011年1月1日至2023年9月12日进行的3期临床试验中提取Kaplan-Meier曲线。
■测试NALIRIFOX的3期临床试验，FOLFIRINOX,选择GEM-NABP或GEM-NABP作为转移性PDAC的一线治疗,并选择报告的总生存期(OS)和无进展生存期(PFS)曲线.本研究遵循了个人参与者数据报告指南的系统审查和荟萃分析的首选报告项目。
■通过图形重建算法从原始试验的Kaplan-Meier图中提取个体患者OS和PFS数据。还收集了总反应率（ORR）和3级或更高的毒性作用率。进行了汇总分析，结果通过网络荟萃分析进行验证.
■主要终点是OS。次要结果包括PFS，ORR,和毒性效应率。
■共分析了2581名患者的7项试验数据，包括383名接受NALIRIFOX治疗的患者，433例接受FOLFIRINOX治疗的患者，1756例患者接受GEM-NABP治疗。接受NALIRIFOX（7.4[95%CI，6.1-7.7]个月）或FOLFIRINOX（7.3[95%CI，6.5-7.9]个月；[HR]，1.21[95%CI，0.86-1.70]；P=.28）与GEM-NABP治疗的患者相比（5.7[95%CI，5.6-6.1]个月；HR与NALIIFOX，1.45[95%CI，1.22-1.73]；P<.001）。同样，GEM-NABP与NALIRIFOX（HR，1.18[95%CI，1.00-1.39]；P=0.05]，而FOLFIRINOX(11.7[95%CI,10.4-13.0]个月)和NALIIFOX(11.1[95%CI,10.1-12.3]个月;HR,1.06[95%CI，0.81-1.39]；P=.65）。NALIIFOX之间的ORR差异无统计学意义（41.8％），FOLFIRINOX（31.6％），和创业板-NABP（35.0%）。NALIRIFOX与较低的3级或更高的血液学毒性作用发生率相关（例如，血小板计数下降1.6%vsFOLFIRINOX的11.8%和GEM-NABP的10.8%)，但与GEM-NABP相比，严重腹泻的发生率更高（20.3％vs15.7％）。
■在本系统综述和荟萃分析中，NALIRIFOX和FOLFIRINOX与一线治疗晚期PDAC的PFS和OS相似，尽管NALIRIFOX与不同的毒性特征相关。精心挑选病人,金融毒性影响的考虑，FOLFIRINOX和NALIIFOX之间的直接比较是必要的。
