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.

Abstract

4052 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/m2 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/m2 on d1; capecitabine 1000 mg/m2, 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.