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.
- Author:
Charles S FUCHS
1
;
Kei MURO
;
Jiri TOMASEK
;
Eric VAN CUTSEM
;
Jae Yong CHO
;
Sang Cheul OH
;
Howard SAFRAN
;
György 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
Author Information
- Publication Type:Original Article
- Keywords: Prognosis; Stomach neoplasms; Gastroesophageal junction; Survival
- MeSH: Adenocarcinoma; Alkaline Phosphatase; Appetite; Aspartate Aminotransferases; Clinical Decision-Making; Disease Progression; Double-Blind Method; Drug Therapy; Esophagogastric Junction; Factor Analysis, Statistical*; Humans; L-Lactate Dehydrogenase; Lymphocytes; Mass Screening; Neoplasm Metastasis; Neutrophils; Prognosis; Proportional Hazards Models; Quality of Life; Sodium; Stomach Neoplasms*
- From:Journal of Gastric Cancer 2017;17(2):132-144
- CountryRepublic of Korea
- Language:English
- 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.
