Efficacy of nab‑paclitaxel vs. Gemcitabine in combination with S‑1 for advanced pancreatic cancer: A multicenter phase II randomized trial

Guo,Xi; Lou,Wenhui; Xu,Yaolin; Zhuang,Rongyuan; Yao,Lie; Wu,Junwei; Fu,Deliang; Zhang,Jun; Liu,Jing; Rong,Yefei; Jin,Dayong; Wu,Wenchuan; Xu,Xuefeng; Ji,Yuan; Wu,Lili; Lv,Minzhi; Yao,Xiuzhong; Liu,Xiaowei; Wang,Dansong; Kuang,Tiantao; Liu,Liang; Wang,Wenquan; Liu,Tianshu; Zhou,Yuhong

doi:10.3892/ol.2024.14293

Efficacy of nab‑paclitaxel vs. Gemcitabine in combination with S‑1 for advanced pancreatic cancer: A multicenter phase II randomized trial

Authors:
- Xi Guo
- Wenhui Lou
- Yaolin Xu
- Rongyuan Zhuang
- Lie Yao
- Junwei Wu
- Deliang Fu
- Jun Zhang
- Jing Liu
- Yefei Rong
- Dayong Jin
- Wenchuan Wu
- Xuefeng Xu
- Yuan Ji
- Lili Wu
- Minzhi Lv
- Xiuzhong Yao
- Xiaowei Liu
- Dansong Wang
- Tiantao Kuang
- Liang Liu
- Wenquan Wang
- Tianshu Liu
- Yuhong Zhou
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Affiliations: Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of General Surgery, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of Pancreatic Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China, Oncology Department, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Pathology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of Radiotherapy, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of Biostatistics, Clinical Research Unit, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of Radiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China, Department of Anti‑tumor Business, Shi Yao Group European Pharmaceutical Co., Ltd., Shijiazhuang, Hebei 050035, P.R. China
Published online on: February 19, 2024 https://doi.org/10.3892/ol.2024.14293
Article Number: 161
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with advanced pancreatic cancer (PC) need a cost‑effective treatment regimen. The present study was designed to compare the efficacy and safety of nab‑paclitaxel plus S‑1 (AS) and gemcitabine plus S‑1 (GS) regimens in patients with chemotherapy‑naïve advanced PC. In this open‑label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy‑naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m² nab‑paclitaxel, days 1 and 8; 80‑120 mg S‑1, days 1‑14) or GS (1,000 mg/m² gemcitabine, days 1 and 8; 80‑120 mg S‑1, days 1‑14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression‑free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow‑up time was 11.37 months [95% confidence interval (CI), 9.31‑13.24]. The median PFS was 7.16 months (95% CI, 5.19‑12.32) for patients treated with AS and 6.41 months (95% CI, 3.72‑8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51‑1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C‑reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

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