A randomized, controlled, multi-center, open-label study of adjuvant nab-paclitaxel plus S-1 (AS) versus capecitabine plus oxaliplatin (CapeOX) for stage III gastric cancer after D2 resection.

person Yu Pengfei Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Hangzhou, China info_outline Yu Pengfei, Yian Du, Zhiyuan Xu, Litao Yang, Jieer Ying, Yongxiang Wang, Ping Chen, Yunhai Wei, Hongtao Xu, Nong Xu, Xiangdong Cheng

Authors person Yu Pengfei Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Hangzhou, China info_outline Yu Pengfei, Yian Du, Zhiyuan Xu, Litao Yang, Jieer Ying, Yongxiang Wang, Ping Chen, Yunhai Wei, Hongtao Xu, Nong Xu, Xiangdong Cheng Organizations Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Hangzhou, China, Ningbo Second Hospital, Ningbo, China, Huzhou Central Hospital (Zhejiang University Huzhou Hospital), Huzhou, China, Lishui Central Hospital, Lishui, China, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: There was no prospective randomized study compared taxanes plus fluoropyrimidine versus platinum plus fluoropyrimidine in adjuvant chemotherapy for advanced gastric cancer. Nab-paclitaxel is nanoparticle albumin-bound formulation, showed a potentially efficacy in gastric cancer. We designed this trial to compare the effective and safety of AS and CapeOX regimen for gastric adenocarcinoma adjuvant therapy. Methods: Patients with stage III gastric or gastroesophageal junction adenocarcinoma who had D2 surgery and achieved R0 resection were randomized 1:1 to AS group and CapeOX. Randomization was stratified by differentiation type (differentiated vs. undifferentiated) and AJCC/UICC pathological stage (IIIA vs. IIIB, IIIC). AS group: Nab-paclitaxel 100 mg/m 2 on d1 and d8; S-1 80-120mg/d, p.o., bid on d1-d14; repeated every 21 days for 8 cycles. CapeOX group: oxaliplatin 130 mg/m 2 on d1; capecitabine 1000 mg/m 2 , p.o., bid on d1-d14; repeated every 21 days for 8 cycles. The primary endpoint is 3-year disease-free survival (3-year-DFS) rate, the secondary endpoints included overall survival (OS), and safety. Results: Between March, 2020 to Jan, 2022, 146 subjects were enrolled to receive either AS regimen (n = 71) or CapeOX regimen (n = 75). The baseline characteristics between two arms were generally balanced. The 1-year DFS rate was 95.50% and 72.84% in AS and CapeOX group, respectively. At the cutoff date, 3 patients (the recurrence sites were peritoneum [n = 1], locoregional [n = 1] and distant [n = 1]) in AS group had relapsed, compared with 10 patients (peritoneum [n = 2], locoregional [n = 4] and distant [n = 4]) in CapeOX group. 4 subjects in CapeOX group died compared with 0 in AS group. A total of 42 patients (AS, n = 21 [29.58%]; CapeOX, n = 21 [28.00%]) needed dose reduction main due to hematological toxicity. The median relative dose intensity of Nab-paclitaxel, S-1, oxaliplatin and capecitabine was 82.55%, 91.30%%, 83.16%% and 78.95%, respectively. Treatments were delayed in 82 of 297 (27.61%, 24 due to hematological and 15 due to non-hematological toxicity) cycles at AS group and in 100 of 319 (31.35%, 18 due to hematological and 13 due to non-hematological toxicity) cycles at CapeOX group. There were 34 (47.89%) patients in AS group and 30 (40.00%) patients in CapeOX group occurred treatment-related adverse events (TRAEs), though most of them were grade I-II. Main grade III-IV AEs were neutropenia (28.16% in AS group vs 8.00% in CapeOX group), leucopenia (15.49% vs 1.33%), thrombocytopenia (0% vs 8.00%) and anemia (5.63% vs 1.33%). Conclusions: Adjuvant AS regimen showed a trend towards better DFS compared with CapeOX regimen, and is a potentially regimen for stage III gastric cancer after curative D2 gastrectomy, with tolerable toxicity. Long-term survival benefit requires more data. Clinical trial information: NCT04135781.