Docetaxel plus S-1 versus cisplatin plus S-1 in unresectable gastric cancer without measurable lesions: a randomized phase II trial (HERBIS-3)

Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80–120 mg on days 1–14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80–120 mg on days 1–21, every 5 weeks). The primary endpoint was overall survival (OS). All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2–49) with DS and 5.5 (range 1–10) with CS. There were no treatment-related deaths. The most common grade 3–4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337–1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.