Real-world comparative effectiveness of FOLFIRINOX versus gemcitabine/nab-paclitaxel in metastatic pancreatic cancer: prognostic impact of metastatic site and burden in a Middle Eastern cohort.

Background: Pancreatic cancer (PC) is one of the most aggressive cancers, with low survival rates. Although FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) are standard first-line treatments, there is a lack of comparative real-world data from Middle Eastern populations, as well as the prognostic significance of metastatic patterns. The study aims to examine the efficacy and toxicity of FFX and GnP in advanced and metastatic PC, as well as assess how the site and number of metastases affect survival outcomes. Methods: This retrospective cohort analysis comprised 60 patients with advanced or metastatic PC treated at a tertiary center from 2019 to 2024. Patients were given either FFX (n=36) or GnP (n=24). The baseline clinicopathologic data, treatment response, toxicity, and survival outcomes were evaluated with SPSS v29. Survival was assessed using Kaplan-Meier and compared using the log-rank test. Variables with P<0.10 in univariate analysis were added to multivariable Cox regression models. Results: The demographic and clinical characteristics of patients treated with FFX and GnP were generally comparable between the two groups. In comparison to patients on GnP, those who received FFX had a slightly longer treatment duration and a substantially higher number of treatment cycles. Patients who received GnP experienced significantly more hematologic adverse events than those who received FFX. In terms of treatment response, FFX demonstrated a higher objective response rate (ORR) and disease control rate (DCR) than GnP. The metastatic site significantly influenced both overall survival (OS) and progression-free survival (PFS) survival outcomes. Kaplan-Meier curves indicate that patients with hepatic involvement experience disease progression and mortality at an earlier stage than those with nodal or other metastatic site. The number of metastatic sites did not exhibit a significant correlation with OS and PFS. In general, lung metastasis consistently demonstrated a favorable prognosis. Conclusions: In this real-world Middle Eastern group, survival outcomes were comparable between FEX and GnP. The metastatic site, particularly lung involvement, emerged as a critical prognostic predictor, implying biological heterogeneity among metastatic PC subtypes and underlining the importance of metastatic pattern in clinical prognosis.