A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus cisplatin with concurrent thoracic radiotherapy for unresectable, locally advanced non-small cell lung cancer: WJOG5008L

Abstract

Background: Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy.

Methods: Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420).

Results: From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm.

Conclusions: The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Fig. 1

Treatment schedule. The treatment schedule of each arm. SP arm: S-1 plus cisplatin plus thoracic radiotherapy (TRT), VP arm: vinorelbine (VNR) plus cisplatin plus thoracic radiotherapy

Fig. 2

Relationship between lung V20 and radiation pneumonitis. The relationship between lung V20 and pneumonitis grading in the SP arm (S-1 plus cisplatin plus thoracic radiotherapy) and the VP arm (vinorelbine plus cisplatin plus thoracic radiotherapy). The patients are arranged in ascending order of V20 on the vertical axis and lung V20 is plotted on the horizontal axis; the grade of pneumonitis is colour coded

Fig. 3

Survival curves. Kaplan–Meier estimates of a overall survival (OS; primary endpoint) in the full analysis set (FAS) and b progression-free survival (PFS) in the FAS. OS was measured from the date of random assignment to the date of death as a result of any cause. At the cutoff date for data inclusion in the analysis, if a patient had not died, OS was censored at the last date they were known to still be alive. PFS was measured from the date of random assignment to the first date of documented objective progression of disease, or of death as a result of any cause. PFS was censored at the date of the last objective progression-free disease assessment before the date of any subsequent systemic anticancer therapy or death, whichever applied first. CI confidence interval, SP arm S-1 plus cisplatin plus thoracic radiotherapy, VP arm vinorelbine plus cisplatin plus thoracic radiotherapy

Fig. 4

Subset analysis. Overall survival hazard ratio in subgroups according to baseline characteristics. CI confidence interval, ECOG PS Eastern Cooperative Oncology Group performance status, CDDP cisplatin, VNR vinorelbine