Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: A randomised phase III trial (TCOG GI-0801/BIRIP trial)

Purpose We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC). Methods Patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan 60 mg/m² plus cisplatin 30 mg/m ², every 2 weeks) or irinotecan alone (irinotecan 150 mg/m ², every 2 weeks). The primary end-point was to show the superiority of BIRIP to irinotecan in terms of progression free survival (PFS). Results 130 patients were enrolled. PFS was significantly longer in the BIRIP group (3.8 months [95% confidence interval (CI) 3.0-4.7]) than in the irinotecan group (2.8 months [2.1-3.3]; hazard ratio 0.68, 95% CI 0.47-0.98; P = 0.0398). Median overall survival was 10.7 months in the BIRIP group and 10.1 months in the irinotecan group (HR 1.00, 95% CI 0.69-1.44, P = 0.9823). The objective response rate was 22% in the BIRIP group and 16% in the irinotecan group (P = 0.4975). However, the disease control rate was significantly better in the BIRIP group (75%) than in the irinotecan group (54%, P = 0.0162). The incidences of grade 3 or worse adverse events did not differ between the two groups. Any grade elevation of serum creatinine was more common in the BIRIP group (25% versus 8%, P = 0.009), but any grade diarrhoea (17% versus 42%, P = 0.002) was more common in the irinotecan group. Conclusion BIRIP significantly prolonged PFS as compared with irinotecan alone and was tolerated as SLC, but did not demonstrate the survival benefit in this trial.