TY - JOUR
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, György
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
N1 - Funding Information:
This research was supported by Eli Lilly and Company, Indianapolis, IN, USA.
Publisher Copyright:
© 2017. Korean Gastric Cancer Association.
PY - 2017/6
Y1 - 2017/6
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
UR - http://www.scopus.com/inward/record.url?scp=85022006266&partnerID=8YFLogxK
U2 - 10.5230/jgc.2017.17.e16
DO - 10.5230/jgc.2017.17.e16
M3 - Article
AN - SCOPUS:85022006266
SN - 2093-582X
VL - 17
SP - 132
EP - 144
JO - Journal of Gastric Cancer
JF - Journal of Gastric Cancer
IS - 2
ER -