Platinum-based combination chemotherapy is a standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has been demonstrated to have a good efficacy with less toxicity for advanced NSCLC treatment. S-1 might be also useful in the adjuvant setting for surgical NSCLC.
We performed a phase II randomized open label multi-institutional study in surgical patients with pathological stage IB (T > 5 cm), II or III NSCLC (7th TNM classification), who underwent complete resection from 2009 to 2013. One hundred and thirty-nine patients were randomly assigned to two arms: S-1 80mg/m2 oral, day1 to 14, q3w, 1year (arm A, n = 70) or S-1 80mg/m2 oral day1 to 21, q5w + cisplatin 60mg/m2 day8, q5w, 4 courses, followed by S-1 80mg/m2 oral day1 to 14, q3w, total 1year (arm B, n = 69). The primary endpoint was the disease free survival (DFS) rate at 2 years and was evaluated using Bayesian method. Either treatment arm would deserve further study if the Bayesian posterior probability that the 2-year DFS rate would exceed a value of 40% were more than 0.85. The secondary endpoints were overall survival (OS), safety, and feasibility.
The clinical characteristics of the patients were well balanced in terms of age, sex and pathological stage between the two arms. The DFS rate at 2 years was 51.4% (95% confidence interval [CI], 0.399–0.628) in arm A and 59.4% (95% CI, 0.476 – 0.702) in arm B. Both treatment arms met the primary endpoint: the probability of a DFS rate ≥ 40% at 2 years was over 0.97 in Arm and 1 in arm B. Neither DFS nor OS were significantly different (log-rank test; p = 0.1695 and p = 0.8684, respectively). No treatment-related deaths were observed in either treatment. The main G3/4 adverse events were appetite loss (arm A vs. arm B, 4.3% vs. 11.6%) and anemia (0% vs. 5.8%), which were not statistically different between the two arms. Treatment completion rate did not differ between the two arms (arm A vs. arm B: 45.7% [95% CI, 41.9–66.3%] vs. 43.5% [95% CI, 44.0–68.4%]).
Oral S-1 based adjuvant chemotherapy was feasible and promising for patients with completely resected NSCLC.
Clinical trial identification
Legal entity responsible for the study
Kyushu University Lung Surgery Study Group
All authors have declared no conflicts of interest.