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Fuchs CS, Muro K, Tomasek J, et al. 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. J Gastric Cancer. 2017;17(2):132-144doi: 10.5230/jgc.2017.17.e16.
Fuchs, C. S., Muro, K., Tomasek, J., Van Cutsem, E., Cho, J. Y., Oh, S. C., Safran, H., Bodoky, G., Chau, I., Shimada, Y., Al-Batran, S. E., Passalacqua, R., Ohtsu, A., Emig, M., Ferry, D., Chandrawansa, K., Hsu, Y., Sashegyi, A., Liepa, A. M., & 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, 17(2), 132-144. https://doi.org/10.5230/jgc.2017.17.e16
Fuchs, Charles S, et al. "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. 17,2 (2017): 132-144. doi: https://doi.org/10.5230/jgc.2017.17.e16
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. 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. J Gastric Cancer. 2017 Jun;17(2):132-144. doi: 10.5230/jgc.2017.17.e16. Epub 2017 Jun 16. PMID: 28680718; PMCID: PMC5489542.
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J Gastric Cancer. 2017 Jun;17(2):132-144. doi: 10.5230/jgc.2017.17.e16. Epub 2017 Jun 16.

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

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

Affiliations

  1. Dana-Farber Cancer Institute, Boston, MA, USA.
  2. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
  3. Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  4. University Hospital Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
  5. Gangnam Severance Hospital, Seoul, Korea.
  6. Korea University Guro Hospital, Seoul, Korea.
  7. Oncology Research Group, Brown University, Providence, RI, USA.
  8. Szent László Hospital, Budapest, Hungary.
  9. Royal Marsden Hospital, London and Surrey, United Kingdom.
  10. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
  11. Institute of Clinical Research, Universitären Centrum für Tumorerkrankungen-University Cancer Center, Frankfurt, Germany.
  12. Istituti Ospitalieri di Cremona, Cremona, Italy.
  13. Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
  14. Lilly Deutschland GmbH, Bad Homburg, Germany.
  15. Eli Lilly and Company, Bridgewater, NJ, USA.
  16. Eli Lilly and Company, Indianapolis, IN, USA.
  17. Departments of Oncology and Hematology with Integrated Palliative Care, Kliniken Essen-Mitte, Essen, Germany.

PMID: 28680718 PMCID: PMC5489542 DOI: 10.5230/jgc.2017.17.e16

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.

Keywords: Gastroesophageal junction; Prognosis; Stomach neoplasms; Survival

Conflict of interest statement

Conflict of Interest: Drs. Emig, Ferry, Chandrawansa, Hsu, Sashegyi, and Liepa are full-time employees and stockholders of Eli Lilly and Company. Dr. Ferry additionally received honoraria from Eli Lil

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