As reported in The Lancet Oncology by Kang et al, the Japanese-Korean phase III SOLAR trial showed that oral tegafur/gimeracil/oteracil, a combination known as S-1, plus leucovorin and oxaliplatin was associated with a modest but significant improvement in overall survival vs S-1 plus cisplatin in the first-line treatment of advanced gastric cancer.

Study Details

In the open-label trial, 711 patients were randomly assigned between January 2015 and December 2016 to receive S-1/leucovorin plus oxaliplatin (n = 356) or S-1 plus cisplatin (n = 355). The primary analysis population included 347 eligible patients in the S-1/leucovorin and oxaliplatin group and 334 in the S-1 plus cisplatin group. Treatment consisted of S-1 (40–60 mg) plus leucovorin (25 mg orally twice daily for 7 days) with oxaliplatin (85 at mg/m² on day 1) every 2 weeks, or S-1 (40–60 mg orally twice daily) for 21 days plus cisplatin (60 mg/m² on day 1 or 8) every 5 weeks.

The primary endpoint was overall survival in the primary analysis population.

Survival

Median follow-up was 26.0 months. Median overall survival was 16.0 months (95% confidence interval [CI] = 13.8–18.3 months) in the S-1/leucovorin plus oxaliplatin group vs 15.1 months (95% CI = 13.6–16.4 months) in the S-1 plus cisplatin group (hazard ratio [HR] = 0.83, 95% CI = 0.69–0.99, P = .039). Hazard ratios consistently favored S-1/leucovorin plus oxaliplatin across all subgroups examined. Poststudy treatment was administered to 82% vs 86% of patients.

Median progression-free survival was 7.1 months (95% CI = 6.8–8.3 months) vs 6.4 months (95% CI = 5.6–6.9 months, HR = 0.79, P = .0045). Among 211 vs 212 patients evaluable for tumor response, objective response was observed in 73% vs 53%, with complete response in 3% vs 3%, and stable disease was observed in an additional 20% vs 38%.  

Adverse Events

The most common grade ≥ 3 adverse events in the S-1/leucovorin plus oxaliplatin group and S-1 plus cisplatin group were anemia (16% vs 18%), neutropenia (15% vs 25%), decreased appetite (15% vs 13%), diarrhea (9% vs 4%), and peripheral sensory neuropathy (9% vs < 1%). Serious adverse events occurred in 44% vs 46% of patients and were considered treatment-related in 26% vs 20%; the most common treatment-related serious adverse event in both groups was decreased appetite (10% vs 7%). Two deaths—both in the S-1/leucovorin plus oxaliplatin group—were considered treatment-related, with causes consisting of pulmonary tuberculosis and viral pneumonia.

The investigators concluded, “[S-1/leucovorin] plus oxaliplatin showed a clinically meaningful improvement in efficacy compared with S-1 plus cisplatin, and could be considered a new first-line treatment option for advanced gastric cancer in Asian patients.”

Narikazu Boku, MD, of the Division of Gastrointestinal Medical Oncology, National Cancer Centre Hospital, Tokyo, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Taiho Pharmaceutical and Yakult Honsha. For full disclosures of the study authors, visit thelancet.com.