Everolimus for previously treated advanced gastric cancer

Results of the randomized, double-blind, phase III GRANITE-1 study

Atsushi Ohtsu, Jaffer A. Ajani, Yu Xian Bai, Yung Jue Bang, Hyun Cheol Chung, Hong Ming Pan, Tarek Sahmoud, Lin Shen, Kun Huei Yeh, Keisho Chin, Kei Muro, Yeul Hong Kim, David Ferry, Niall C. Tebbutt, Salah Eddin Al-Batran, Heind Smith, Chiara Costantini, Syed Rizvi, David Lebwohl, Eric Van Cutsem

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3935-3943
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number31
DOIs
Publication statusPublished - 2013 Nov 1

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Stomach Neoplasms
Safety
Placebos
Drug Therapy
Disease-Free Survival
Survival
Everolimus
Appetite
Sirolimus
Random Allocation
Fatigue
Disease Progression
Anemia
Appointments and Schedules
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Everolimus for previously treated advanced gastric cancer : Results of the randomized, double-blind, phase III GRANITE-1 study. / Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu Xian; Bang, Yung Jue; Chung, Hyun Cheol; Pan, Hong Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric.

In: Journal of Clinical Oncology, Vol. 31, No. 31, 01.11.2013, p. 3935-3943.

Research output: Contribution to journalArticle

Ohtsu, A, Ajani, JA, Bai, YX, Bang, YJ, Chung, HC, Pan, HM, Sahmoud, T, Shen, L, Yeh, KH, Chin, K, Muro, K, Kim, YH, Ferry, D, Tebbutt, NC, Al-Batran, SE, Smith, H, Costantini, C, Rizvi, S, Lebwohl, D & Van Cutsem, E 2013, 'Everolimus for previously treated advanced gastric cancer: Results of the randomized, double-blind, phase III GRANITE-1 study', Journal of Clinical Oncology, vol. 31, no. 31, pp. 3935-3943. https://doi.org/10.1200/JCO.2012.48.3552
Ohtsu, Atsushi ; Ajani, Jaffer A. ; Bai, Yu Xian ; Bang, Yung Jue ; Chung, Hyun Cheol ; Pan, Hong Ming ; Sahmoud, Tarek ; Shen, Lin ; Yeh, Kun Huei ; Chin, Keisho ; Muro, Kei ; Kim, Yeul Hong ; Ferry, David ; Tebbutt, Niall C. ; Al-Batran, Salah Eddin ; Smith, Heind ; Costantini, Chiara ; Rizvi, Syed ; Lebwohl, David ; Van Cutsem, Eric. / Everolimus for previously treated advanced gastric cancer : Results of the randomized, double-blind, phase III GRANITE-1 study. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 31. pp. 3935-3943.
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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.",
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AU - Ajani, Jaffer A.

AU - Bai, Yu Xian

AU - Bang, Yung Jue

AU - Chung, Hyun Cheol

AU - Pan, Hong Ming

AU - Sahmoud, Tarek

AU - Shen, Lin

AU - Yeh, Kun Huei

AU - Chin, Keisho

AU - Muro, Kei

AU - Kim, Yeul Hong

AU - Ferry, David

AU - Tebbutt, Niall C.

AU - Al-Batran, Salah Eddin

AU - Smith, Heind

AU - Costantini, Chiara

AU - Rizvi, Syed

AU - Lebwohl, David

AU - Van Cutsem, Eric

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N2 - 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.

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