Adjuvant S-1 + oxaliplatin yields survival benefit in G/GEJ cancer

Combining S-1 and oxaliplatin (SOX) as an adjuvant chemotherapy significantly improves overall survival (OS) and disease-free survival (DFS) compared with S-1 alone in patients with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, according to the final results of the CAPITAL trial presented at ASCO GI 2026.

“In Asia, adjuvant S-1 monotherapy following D2 gastrectomy represents a standard treatment for patients with pathological stage II/III G/GEJ,” said lead author Dr Run-Cong Nie from Sun Yat-sen University Cancer Centre in Guangzhou, China.

“It is also expected that combination therapy, such as docetaxel/oxaliplatin plus S-1, may further improve efficacy,” he stated.

Hence, Nie and his team sought to assess the efficacy and safety of the SOX regimen in this patient population.

This phase III, multicentre, open-label trial enrolled 724 patients with stage II–III G/GEJ adenocarcinoma who had undergone D2 gastrectomy at 13 centres in China. Participants were randomized in a 1:1 ratio to receive either the SOX regimen (six cycles of SOX, followed by 10 cycles of S-1) or S-1 monotherapy (16 cycles with a 1-week rest period).

At a median follow-up of 74 months, patients treated with SOX achieved a significantly higher 5-year OS rate compared with those receiving S-1 alone (70.9 percent vs 62.9 percent; hazard ratio [HR], 0.74; p=0.018). [ASCO GI 2026, abstract 289]

The combination therapy arm also demonstrated significantly higher DFS rates at 3 (71.2 percent vs 65.1 percent) and 5 years (66.2 percent vs 55.6 percent; HR, 0.76; p=0.021) compared with the S-1 monotherapy arm.

The OS benefit observed with the SOX regimen was consistent across all key subgroups, including age, sex, ECOG PS, pathological stage, and Lauren classification, said Nie.

In terms of safety, patients in the SOX arm experienced a slightly higher rate of grade 3–4 treatment-related adverse events (AEs) than those in the S-1 alone arm (25 percent vs 13 percent).

The most common AEs reported in the SOX arm were neutropenia (13 percent), followed by anaemia and nausea (4 percent for both), but Nie noted that these AEs were mostly manageable, and no treatment-related deaths occurred.

Additionally, the SOX regimen was associated with a lower rate of first relapse (24 percent vs 31 percent), with the most notable reduction observed in locoregional recurrence (2 percent vs 7 percent), compared with S-1 monotherapy.

Overall, “the CAPITAL trial supports the SOX regimen as a standard adjuvant treatment for this population following D2 gastrectomy,” Nie concluded.