Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study

Abstract

Purpose: The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer.

Patients and methods: Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety.

Results: Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW.

Conclusion: Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers.

Trial registration: ClinicalTrials.gov NCT00879333.

Fig 1.

CONSORT diagram. (*) Patients could be excluded for more than one reason. BSC, best supportive care.

Fig 2.

Overall and progression-free survival for all randomly assigned patients. (A) Kaplan-Meier plot of overall survival. (B) Forest plot of overall survival in subgroups. (C) Kaplan-Meier plot of progression-free survival. (D) Longitudinal mean scores of the global health status/quality-of-life scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. ECOG PS, European Cooperative Oncology Group performance status; GE, gastroesophageal; n, number of patients with event (of the number of patients at risk); ROW, rest of world. Appendix Table A3 (online only) lists details on the events experienced.

Fig 2.

Overall and progression-free survival for all randomly assigned patients. (A) Kaplan-Meier plot of overall survival. (B) Forest plot of overall survival in subgroups. (C) Kaplan-Meier plot of progression-free survival. (D) Longitudinal mean scores of the global health status/quality-of-life scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. ECOG PS, European Cooperative Oncology Group performance status; GE, gastroesophageal; n, number of patients with event (of the number of patients at risk); ROW, rest of world. Appendix Table A3 (online only) lists details on the events experienced.

Fig 2.

Overall and progression-free survival for all randomly assigned patients. (A) Kaplan-Meier plot of overall survival. (B) Forest plot of overall survival in subgroups. (C) Kaplan-Meier plot of progression-free survival. (D) Longitudinal mean scores of the global health status/quality-of-life scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. ECOG PS, European Cooperative Oncology Group performance status; GE, gastroesophageal; n, number of patients with event (of the number of patients at risk); ROW, rest of world. Appendix Table A3 (online only) lists details on the events experienced.