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. 2023 Aug 29;20(10):765-778.
doi: 10.20892/j.issn.2095-3941.2023.0189.

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma

Zhou Zhu #  1   2 , Hui Tang #  1 , Jinrong Ying  1 , Yuejuan Cheng  1 , Xiang Wang  1 , Yingyi Wang  1 , Chunmei Bai  1
Affiliations

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma

Zhou Zhu et al. Cancer Biol Med. .

Abstract

Objective: Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC.

Methods: Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated.

Results: A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049).

Conclusions: As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

Keywords: Advanced pancreatic cancer; S-1; first-line chemotherapy; gemcitabine; nab-paclitaxel.

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Conflict of interest statement

No potential conflicts of interest are disclosed.

Figures

Figure 1
Figure 1
Kaplan-Meier curves of overall survival (A) and progression-free survival (B) for all patients.
Figure 2
Figure 2
Kaplan-Meier curves of overall survival (A) and progression-free survival (B) for matched patients.
Figure 3
Figure 3
Forest plot of overall survival in the selected subgroups.
Figure 4
Figure 4
Forest plot of progression-free survival in the selected subgroups.
Figure 5
Figure 5
Schematic of the mechanisms of GS and GnP. For GS, S-1 is an oral derivative of the 5-FU prodrug combined with 2 modulators. The expression of hENT1, the mediator of gemcitabine uptake, is upregulated by 5-FU. For GnP, nab-paclitaxel increases gemcitabine levels by inhibiting the gemcitabine-metabolizing enzyme cytidine deaminase. FT, tegafur; CDHP, gimeracil; Oxo, oteracil.
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