RESOLVE: Significant Improvement in 3-Year Disease-Free Survival with Use of Perioperative SOX in Patients with Locally Advanced Gastric Cancer

2021 Year in Review - Gastrointestinal Cancer

Perioperative SOX treatment significantly improved 3-year disease-free survival in patients with locally advanced gastric cancer compared with adjuvant CapOx.

Gastric cancer is often diagnosed at an advanced stage when treatment options are often palliative. East Asia has the highest incidence of gastric cancer, with South America and some European countries also having high incidence rates. Prognosis of advanced gastric cancer is poor and there is an unmet need for improved treatment strategies. Standard of treatment for locally advanced cancer is multimodal, including gastrectomy and chemotherapy or chemoradiation, with debate about the sequencing of surgery and ongoing chemotherapy. Perioperative chemotherapy for patients with cT2-4 or N+ and M0 tumors with either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is recommended by the National Comprehensive Cancer Network and European guidelines. CapOx (capecitabine plus oxaliplatin) is recommended for postoperative chemotherapy. S-1 is an oral derivative of fluoropyrimidine that has fewer adverse events (AEs) compared with fluorouracil and has demonstrated efficacy when combined with oxaliplatin and cisplatin.

The RESOLVE clinical trial compared perioperative or postoperative S-1 plus oxaliplatin (SOX) with postoperative CapOx in patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma undergoing D2 gastrectomy. This was an open-label, phase 3 randomized trial, performed across 27 hospitals in China, of 1022 adult patients with treatment-naïve confirmed cT4a N+ M0 or cT4b Nany M0 gastric or GEJ cancer. Patients were randomized to receive adjuvant CapOx, adjuvant SOX, or perioperative SOX, with treatment initiated within 2 weeks of randomization.

The CapOx group started therapy 4 to 8 weeks after surgery. Patients received 130 mg/m2 via infusion plus 1000 mg/m2 oral capecitabine twice daily for 2 weeks, then 1 week of rest, for 8 treatment cycles. The adjuvant SOX group also started therapy 4 to 8 weeks post-surgery for 8 treatment cycles of 21-day lengths. On day 1, patients received 130 mg/m2 oxaliplatin plus oral S-1 dosed according to body surface: <1.25 m2, 40 mg; 1.25 to 1.5 m2, 50 mg; and >1.5 m2, 60 mg, all dosed twice daily for 2 weeks, followed by 1 week of rest. The perioperative SOX group had the same regimen as the adjuvant SOX group, with 3 cycles 3 to 6 weeks prior to surgery, and the remaining 5 cycles 4 to 8 weeks after surgery, then 3 cycles of S-1 monotherapy.

The 3-year disease-free survival rate was 51.1% in the CapOx group, 56.5% in the adjuvant SOX group, and 59.4% in the perioperative SOX group. When AEs were evaluated, the most common grade 3 to 4 AE was neutropenia in all groups. The only significant difference in AEs was that grade 3 to 4 thrombocytopenia and anemia were higher in the perioperative SOX group when compared with the adjuvant CapOx group. Serious AEs were reported in 2% to 3% of each study group.

The significant 3-year disease-free survival for patients receiving perioperative SOX treatment is encouraging.

Source: Zhang X, Liang H, Li Z, et al. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021;22:1081-1092.

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