Prognostic factor analysis of overall survival in gastric cancer from two phase iii studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data

Charles S. Fuchs, Kei Muro, Jiri Tomasek, Eric Van Cutsem, Jae Yong Cho, Sang Cheul Oh, Howard Safran, G. Bodoky, Ian Chau, Yasuhiro Shimada, Salah Eddin Al-Batran, Rodolfo Passalacqua, Atsushi Ohtsu, Michael Emig, David Ferry, Kumari Chandrawansa, Yanzhi Hsu, Andreas Sashegyi, Astra M. Liepa, Hansjochen Wilke

Research output: Contribution to journalArticle

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Abstract

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/ or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

Original languageEnglish
Pages (from-to)132-144
Number of pages13
JournalJournal of Gastric Cancer
Volume17
Issue number2
DOIs
Publication statusPublished - Jun 1 2017

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Statistical Factor Analysis
Stomach Neoplasms
Survival
Proportional Hazards Models
Esophagogastric Junction
Disease Progression
Stomach
Quality of Life
Therapeutics
Neoplasms
Appetite
Aspartate Aminotransferases
Platinum
L-Lactate Dehydrogenase
Double-Blind Method
Alkaline Phosphatase
ramucirumab
Albumins
Adenocarcinoma
Neutrophils

Keywords

  • Gastroesophageal junction
  • Prognosis
  • Stomach neoplasms
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Prognostic factor analysis of overall survival in gastric cancer from two phase iii studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data. / Fuchs, Charles S.; Muro, Kei; Tomasek, Jiri; Van Cutsem, Eric; Cho, Jae Yong; Oh, Sang Cheul; Safran, Howard; Bodoky, G.; Chau, Ian; Shimada, Yasuhiro; Al-Batran, Salah Eddin; Passalacqua, Rodolfo; Ohtsu, Atsushi; Emig, Michael; Ferry, David; Chandrawansa, Kumari; Hsu, Yanzhi; Sashegyi, Andreas; Liepa, Astra M.; Wilke, Hansjochen.

In: Journal of Gastric Cancer, Vol. 17, No. 2, 01.06.2017, p. 132-144.

Research output: Contribution to journalArticle

Fuchs, CS, Muro, K, Tomasek, J, Van Cutsem, E, Cho, JY, Oh, SC, Safran, H, Bodoky, G, Chau, I, Shimada, Y, Al-Batran, SE, Passalacqua, R, Ohtsu, A, Emig, M, Ferry, D, Chandrawansa, K, Hsu, Y, Sashegyi, A, Liepa, AM & Wilke, H 2017, 'Prognostic factor analysis of overall survival in gastric cancer from two phase iii studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data', Journal of Gastric Cancer, vol. 17, no. 2, pp. 132-144. https://doi.org/10.5230/jgc.2017.17.e16
Fuchs, Charles S. ; Muro, Kei ; Tomasek, Jiri ; Van Cutsem, Eric ; Cho, Jae Yong ; Oh, Sang Cheul ; Safran, Howard ; Bodoky, G. ; Chau, Ian ; Shimada, Yasuhiro ; Al-Batran, Salah Eddin ; Passalacqua, Rodolfo ; Ohtsu, Atsushi ; Emig, Michael ; Ferry, David ; Chandrawansa, Kumari ; Hsu, Yanzhi ; Sashegyi, Andreas ; Liepa, Astra M. ; Wilke, Hansjochen. / Prognostic factor analysis of overall survival in gastric cancer from two phase iii studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data. In: Journal of Gastric Cancer. 2017 ; Vol. 17, No. 2. pp. 132-144.
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abstract = "Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/ or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93{\%}) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95{\%} confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.",
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T1 - Prognostic factor analysis of overall survival in gastric cancer from two phase iii studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data

AU - Fuchs, Charles S.

AU - Muro, Kei

AU - Tomasek, Jiri

AU - Van Cutsem, Eric

AU - Cho, Jae Yong

AU - Oh, Sang Cheul

AU - Safran, Howard

AU - Bodoky, G.

AU - Chau, Ian

AU - Shimada, Yasuhiro

AU - Al-Batran, Salah Eddin

AU - Passalacqua, Rodolfo

AU - Ohtsu, Atsushi

AU - Emig, Michael

AU - Ferry, David

AU - Chandrawansa, Kumari

AU - Hsu, Yanzhi

AU - Sashegyi, Andreas

AU - Liepa, Astra M.

AU - Wilke, Hansjochen

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/ or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

AB - Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/ or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

KW - Gastroesophageal junction

KW - Prognosis

KW - Stomach neoplasms

KW - Survival

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