S-1 plus oxaliplatin versus S-1 plus cisplatin as first-line treatment for advanced diffuse-type or mixed-type gastric/gastroesophageal junction adenocarcinoma: A randomized, phase 3 trial.

Abstract

4017 Background: Diffuse-type or mixed-type gastric adenocarcinoma is associated with poor prognosis, and more effective treatment is needed. In Asia, S-1 plus cisplatin (SP) is the standard first-line chemotherapy regimen for advanced gastric cancer. Nevertheless, some clinical data suggested that oxaliplatin-based chemotherapy might be more efficacious and more tolerant than cisplatin-based chemotherapy. Methods: This trial is a multicenter, randomized, parallel-group, open-label, phase 3 trial in China. Patients aged 18-75 years, with PS 0-2, adequate organ function, histology confirmed, unresectable, advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA were randomized 1:1 to S-1 plus oxaliplatin group (SOX) (S-1: 40-60mg bid on d1-14, q3w; oxaliplatin: 130 mg/m2 on d1, q3w) or SP group (S-1: 40-60mg bid on d1-14, q3w; cisplatin: 60 mg/m2 d1, q3w). The primary endpoint was overall survival (OS) in the full analysis set (FAS). The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and safety. Results: Between Jul 2013 and Jul 2018, 576 patients were randomized and 558 initiated treatment (279 patients/group). The median number of chemotherapy cycles was four in each group. In the FAS, the SOX group showed improved OS (13.0 vs. 11.8 months, HR = 0.764, 95% CI: 0.636-0.918), PFS (5.7 vs. 4.9 months, HR = 0.752, 95%CI: 0.632-0.895), and TTF (5.2 vs. 4.7 months, HR = 0.763, 95%CI: 0.641-0.909) compared with the SP group. In terms of grade≥3 adverse events, SOX showed lower occurrences of neutropenia (10.0% vs. 22.9%), leukopenia (9.7% vs. 21.9%), anemia (4.3% vs. 14.3%),vomiting (3.9% vs. 10.4%), nausea (2.2% vs. 10.4%), anorexia (2.2% vs. 6.8%), and febrile neutropenia (2.5% vs. 6.8%) than SP (all P < 0.05). The occurrence of grade≤2 sensory neuropathy(41.6% vs. 12.2%, P < 0.001)was higher with SOX than with SP. Conclusion: Compared with SP, SOX was more effective and less toxic (except neurosensory toxicity ) in patients with previously untreated advanced diffuse-type or mixed-type gastric adenocarcinoma/GEJA. Clinical trial information: NCT01824459.