Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study

Oncologist. 2024 Oct 3;29(10):e1406-e1418. doi: 10.1093/oncolo/oyae171.

Abstract

Background: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC).

Methods: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS).

Results: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group.

Conclusion: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

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

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Albumins* / administration & dosage
  • Albumins* / adverse effects
  • Albumins* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / adverse effects
  • Deoxycytidine* / analogs & derivatives
  • Deoxycytidine* / therapeutic use
  • Drug Combinations*
  • Female
  • Gemcitabine*
  • Humans
  • Male
  • Middle Aged
  • Oxonic Acid* / administration & dosage
  • Oxonic Acid* / adverse effects
  • Oxonic Acid* / therapeutic use
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / adverse effects
  • Paclitaxel* / pharmacology
  • Paclitaxel* / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Tegafur* / administration & dosage
  • Tegafur* / adverse effects
  • Tegafur* / therapeutic use

Substances

  • Gemcitabine
  • Deoxycytidine
  • 130-nm albumin-bound paclitaxel
  • Paclitaxel
  • Tegafur
  • S 1 (combination)
  • Oxonic Acid
  • Albumins
  • Drug Combinations

Associated data

  • ClinicalTrials.gov/NCT03636308