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, 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

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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
Issue number2
Publication statusPublished - 2017 Jun


  • Gastroesophageal junction
  • Prognosis
  • Stomach neoplasms
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research


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