Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

Abstract

Background Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. Methods The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study. Results Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78–1.63; PFS: HR: 1.19; 95% CI: 0.85–1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04–1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. Conclusions The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

The efficacy and safety of Nab-paclitaxel plus gemcitabine versus mFOLFIRINOX in the first-line treatment of metastatic pancreatic cancer: a retrospective study

“…Several retrospective studies have found that there is no significant difference between the two chemotherapy regimens [8][9][10]. Moreover, a network meta-analysis including twenty-two studies in 2021 reported that the survival and toxicity of these two chemotherapy regimens were similar in advanced pancreatic cancer [11]. However, a retrospective study in Korea concluded that FFX would be a better first-line treatment choice than AG as FFX achieved a longer overall survival in metastatic pancreatic cancer [12].…”

Folfirinox vs. Gemcitabine + Nab-Paclitaxel as the First-Line Treatment for Pancreatic Cancer: A Systematic Review and Meta-Analysis

“…2023;14(5):325-339 studies have shown that FFX is likely to be associated with a longer OS when compared to GnP [17,18,27,28,38]. There was no statistical difference found with a longer PFS with the use of FFX or GnP but pooling of studies and a larger number of participants from previous meta-analysis showed that FFX was associated with a longer PFS in contrast to GnP [10]. Safety profiles have differed between the two regimens with a difference of results in multiple studies.…”

“…Furthermore, the previous studies did not evaluate the detailed safety profiles for the two regimens; hence, our meta-analysis, with a larger sample size and excellent statistical power, examined the safety profiles and included the most recent published studies. Importantly, the literature search period for our study extends until February 2023; therefore, our study encompasses recently published randomized controlled trials (RCTs), which were conducted to fill in the literature gap [10]. Lastly, our study has different clinical implications based on patient settings.…”

Predicting the chemosensitivity of pancreatic cancer cells as a personalized therapy

“…Although the differences between OS and PFS for both regimens are statistically insignificant, NPXL+GMC has been shown to be more effective, with indications of less toxicity. [8][9][10] Unfortunately, pancreatic cancer is a chemoresistant disease. This is due to acquired abnormalities in the tumor cell membrane transport protein hENT1, 11 nucleoside enzymes 12,13 and changes in the epithelial-mesenchymal transition.…”