EAST-LC: Randomized controlled phase III trial of S-1 versus docetaxel in patients with non-small-cell lung cancer who had received a platinum-based treatment

Abstract

Background Two phase II studies had evaluated the efficacy and safety of S-1, an oral 5-FU, in patients with previously treated NSCLC. The results of these studies suggested that S-1 was comparable to the docetaxel (DOC), a standard therapy for previously treated NSCLC. This randomized phase III study aims to establish non-inferiority of S-1 monotherapy to DOC in patients with previously treated NSCLC in Asia. Methods Patients with stage IIIB/IV NSCLC who had received at least 1 regimen of platinum-based chemotherapy with/without prior exposure to gefitinib or erlotinib were eligible. Patients were randomized to S-1 (80-120 mg/day on days 1-28 every 42-day) or DOC (60 mg/m2 in Japan, 75 mg/m2 in other countries, on day 1 every 21days). The primary objective was to evaluate whether S-1 is non-inferior to DOC in terms of overall survival (OS) (upper CI limit for HR < 1.2). Secondary objectives include progression-free survival (PFS), time to treatment failure (TTF), response rate (RR), quality of life, and safety. Results Total of 1154 patients were enrolled from 7/2010 to 6/2014; and median follow-up time was 30.75 months. The median OS of the S-1 group was non-inferior to the DOC group (12.75 months versus 12.52 months; hazard ratio [HR] 0.945; 95% confidence interval [CI] 0.833-1.073; P =0.3818). Subgroup analysis by country (Japan vs non-Japan) is summarized in Table. PFS was also similar between the two groups (2.86 months versus 2.89 months). Grade 3 or higher febrile neutropenia and neutropenia were higher in the DOC group (0.9%vs 13.6%; 5.4% vs 47.7% in S1 and DOC group, respective). Other non-hematoloic toxicities in S1 and DOC group are as followed; diarrhea (37.2% versus 18.2%), stomatitis (23.9% versus 14.5%) and decreased appetite (52.6% versus 37.9%), respectively. Japan Non-Japan DOC S-1 DOC S-1 No of Pt 359 361 211 216 MST(m) 12.6 13.4 12.1 10.8 HR (95%CI) 0.922 (0.789-1.079) 1.056 (0.854-1.307) Interaction test P value 0.3374 Conclusions S-1 is non-inferior to DOC in terms of OS, with tolerable toxicity. S-1 monotherapy is one of the treatment options for patients with previously treated NSCLC.