Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer - A randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Background: The value of second-line therapy for metastatic gastric cancer is unclear. So far there are no randomised phase III data comparing second-line chemotherapy to best supportive care (BSC). In this prospective, multicenter, open label, randomised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy. Methods: Eligible patients (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma, objective tumour progression during or within 6 months after first-line chemotherapy and ECOG performance status 0-2. Stratification for time of progression after first-line therapy, ECOG PS and pretreatment secured even distribution of important prognostic factors. Treatment: Arm A: Irinotecan 250 mg/m(2) q3w (first cycle) to be increased to 350 mg/m2(,) depending on toxicity. Arm B: BSC. Findings: Between 10/2002 and 12/2006 40 pts were randomised. The study was closed prematurely due to poor accrual. Response for arm A (19 pts evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25-0.92) in the irinotecan-arm (p = 0.012). Median survival arm A: 4.0 months (95% CI 3.6-7.5), arm B: 2.4 months (95% CI 1.7-4.9). Interpretation: Irinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts. Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer. Funding: The study was supported by a research grant from Aventis and Pfizer. (C) 2011 Elsevier Ltd. All rights reserved.