Everolimus for previously treated advanced gastric cancer: Results of the randomized, double-blind, phase III GRANITE-1 study
Journal
Journal of Clinical Oncology
Journal Volume
31
Journal Issue
31
Pages
3935-3943
Date Issued
2013
Author(s)
Ohtsu A.
Ajani J.A.
Bai Y.-X.
Bang Y.-J.
Chung H.-C.
Pan H.-M.
Sahmoud T.
Shen L.
Chin K.
Muro K.
Kim Y.H.
Ferry D.
Tebbutt N.C.
Al-Batran S.-E.
Smith H.
Costantini C.
Rizvi S.
Lebwohl D.
Van Cutsem E.
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. ? 2013 by American Society of Clinical Oncology.
SDGs
Other Subjects
everolimus; placebo; everolimus; immunosuppressive agent; rapamycin; drug derivative; immunosuppressive agent; rapamycin; abdominal pain; adult; advanced cancer; article; Asia; asthenia; backache; cancer chemotherapy; cancer growth; cancer localization; cancer survival; cerebrovascular accident; chemotherapy induced anemia; chemotherapy induced emesis; chemotherapy induced nausea and vomiting; Chinese; constipation; controlled study; coughing; decreased appetite; diarrhea; double blind procedure; drug blood level; drug dose reduction; drug efficacy; drug eruption; drug exposure; drug fatality; drug intermittent therapy; drug safety; drug tolerability; drug withdrawal; dyspnea; ethnicity; fatigue; female; fever; gastrectomy; gastrointestinal hemorrhage; Hispanic; human; hypokalemia; Indian; insomnia; Japanese; liver metastasis; lower esophagus sphincter; lung metastasis; major clinical study; male; maximum plasma concentration; middle aged; multicenter study; multiple organ failure; neutropenia; overall survival; patient history of chemotherapy; patient history of radiotherapy; patient history of surgery; peripheral edema; phase 3 clinical trial; pneumonia; priority journal; progression free survival; pruritus; randomization; randomized controlled trial; side effect; steady state; stomach cancer; stomatitis; sudden death; systemic therapy; thrombocytopenia; treatment failure; treatment response; treatment withdrawal; upper abdominal pain; weight reduction; adenocarcinoma; aged; analogs and derivatives; clinical trial; disease free survival; Kaplan Meier method; mortality; Neoplasm Recurrence, Local; proportional hazards model; Stomach Neoplasms; very elderly; young adult; adenocarcinoma; controlled clinical trial; stomach tumor; tumor recurrence; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Proportional Hazards Models; Sirolimus; Stomach Neoplasms; Young Adult; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Proportional Hazards Models; Sirolimus; Stomach Neoplasms; Young Adult
Publisher
American Society of Clinical Oncology
Type
journal article