A phase III study of TAS-118 plus oxaliplatin versus S-1 plus cisplatin as first-line chemotherapy in patients with advanced gastric cancer (SOLAR study)

Abstract

Introduction: A fluoropyrimidine plus platinum compound has been used as the standard first‐line chemotherapy for advanced gastric cancer (AGC). TAS‐118 is an oral drug containing S‐1 that is a fluoropyrimidine preparation combining tegafur, a prodrug of 5‐fluorouracil, gimeracil, and oteracil potassium, and leucovorin. A randomized phase II study (S. Hironaka et al, Lancet Oncol. 2016) showed promising activity of S‐1 plus leucovorin and oxaliplatin, compared with S‐1 plus cisplatin in patients (pts) with AGC. We conducted a randomized, open‐label, phase III trial (SOLAR study, NCT02322593) to evaluate the efficacy and safety of TAS‐118 plus oxaliplatin vs. S‐1 plus cisplatin in pts with AGC in Japan and Korea. Methods: This study enrolled pts with histologically confirmed, metastatic or recurrent HER2‐negative gastric cancer, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0/1 and no prior treatment. Pts were randomized 1:1 to receive TAS‐ 118 (S‐1 40‐60 mg and leucovorin 25mg orally bid) for 7 days and oxaliplatin (85 mg/ m2) on day 1 every 2 weeks (TAS‐118 plus oxaliplatin) or S‐1 (40‐60 mg orally bid) for 21 days and cisplatin (60mg/m2) on day 1 (Korea) or day 8 (Japan) every 5 weeks (SP), stratified by ECOG PS, measurable lesion, and country. Primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression free survival (PFS), overall response rate (ORR), and safety. Results: From Jan 2015 to Dec 2016, 711 pts were randomized to either TAS 118 plus oxaliplatin (n=356) or SP (n=355). Eleven pts not receiving the protocol treatment and 19 ineligible pts were excluded from FAS. Baseline characteristics were well balanced between the treatment arms. In the primary analysis with 491 events, median OS was 16.0 months in TAS‐118 plus oxaliplatin and 15.1 months in SP (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.69‐0.99; stratified log‐rank test P=.039). Median PFS was 7.1 months in TAS‐118 plus oxaliplatin and 6.4 months in SP (HR 0.79; 95% CI, 0.66‐0.93; P= .005). ORR in TAS‐118 plus oxaliplatin and SP were 73.5% and 50.0%, respectively (P