Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer

A randomized, double-blind, placebo-controlled phase III study

Atsushi Ohtsu, Manish A. Shah, Eric Van Cutsem, SunYoung Rha, Akira Sawaki, Sook Ryun Park, Ho Yeong Lim, Yasuhide Yamada, Jian Wu, Bernd Langer, Michal Starnawski, Yoon Koo Kang

Research output: Contribution to journalArticle

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Abstract

Purpose: The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. Patients and Methods: Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results: In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine- cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified. Conclusion: Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.

Original languageEnglish
Pages (from-to)3968-3976
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number30
DOIs
Publication statusPublished - 2011 Oct 20

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Combination Drug Therapy
Stomach Neoplasms
Placebos
Cisplatin
Therapeutics
Disease-Free Survival
Survival
Bevacizumab
Appetite
Neutropenia
Fluorouracil
Disease Progression
Anemia
Randomized Controlled Trials
Safety
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ohtsu, Atsushi ; Shah, Manish A. ; Van Cutsem, Eric ; Rha, SunYoung ; Sawaki, Akira ; Park, Sook Ryun ; Lim, Ho Yeong ; Yamada, Yasuhide ; Wu, Jian ; Langer, Bernd ; Starnawski, Michal ; Kang, Yoon Koo. / Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer : A randomized, double-blind, placebo-controlled phase III study. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 30. pp. 3968-3976.
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title = "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study",
abstract = "Purpose: The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. Patients and Methods: Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results: In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine- cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95{\%} CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95{\%} CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0{\%} v 37.4{\%}; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35{\%}, bevacizumab plus fluoropyrimidine-cisplatin; 37{\%}, placebo plus fluoropyrimidine-cisplatin), anemia (10{\%} v 14{\%}), and decreased appetite (8{\%} v 11{\%}). No new bevacizumab-related safety signals were identified. Conclusion: Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.",
author = "Atsushi Ohtsu and Shah, {Manish A.} and {Van Cutsem}, Eric and SunYoung Rha and Akira Sawaki and Park, {Sook Ryun} and Lim, {Ho Yeong} and Yasuhide Yamada and Jian Wu and Bernd Langer and Michal Starnawski and Kang, {Yoon Koo}",
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Ohtsu, A, Shah, MA, Van Cutsem, E, Rha, S, Sawaki, A, Park, SR, Lim, HY, Yamada, Y, Wu, J, Langer, B, Starnawski, M & Kang, YK 2011, 'Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study', Journal of Clinical Oncology, vol. 29, no. 30, pp. 3968-3976. https://doi.org/10.1200/JCO.2011.36.2236

Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer : A randomized, double-blind, placebo-controlled phase III study. / Ohtsu, Atsushi; Shah, Manish A.; Van Cutsem, Eric; Rha, SunYoung; Sawaki, Akira; Park, Sook Ryun; Lim, Ho Yeong; Yamada, Yasuhide; Wu, Jian; Langer, Bernd; Starnawski, Michal; Kang, Yoon Koo.

In: Journal of Clinical Oncology, Vol. 29, No. 30, 20.10.2011, p. 3968-3976.

Research output: Contribution to journalArticle

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T1 - Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer

T2 - A randomized, double-blind, placebo-controlled phase III study

AU - Ohtsu, Atsushi

AU - Shah, Manish A.

AU - Van Cutsem, Eric

AU - Rha, SunYoung

AU - Sawaki, Akira

AU - Park, Sook Ryun

AU - Lim, Ho Yeong

AU - Yamada, Yasuhide

AU - Wu, Jian

AU - Langer, Bernd

AU - Starnawski, Michal

AU - Kang, Yoon Koo

PY - 2011/10/20

Y1 - 2011/10/20

N2 - Purpose: The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. Patients and Methods: Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results: In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine- cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified. Conclusion: Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.

AB - Purpose: The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer. Patients and Methods: Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference. Results: In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine- cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified. Conclusion: Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.

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