Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial

Takayuki Yoshino, Radka Obermannová, György Bodoky, Rocio Garcia-Carbonero, Tudor Ciuleanu, David C. Portnoy, Tae Won Kim, Yanzhi Hsu, David Ferry, Federico Nasroulah, Josep Tabernero

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Abstract

© 2017 The Author(s) Background The RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73–0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters. Methods CEA subgroups (≤10 versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The Kaplan–Meier method estimated the median OS and the progression-free survival (PFS). Log-rank test compared the survival distributions within the subgroups. Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup interaction p-values were calculated by Cox proportional hazards model. Results Ramucirumab treatment prolonged survival for the CEA ≤10 subgroup (HR = 0.68; 95% CI = 0.50–0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76–1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater for the CEA ≤10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus 0.8 months greater, respectively). The interaction P-value between CEA level and treatment effect on OS was 0.088. This trend was observed across randomisation strata and to a lesser extent for PFS (P = 0.594). Conclusions Although patients in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab treatment, the low baseline CEA level may identify a subgroup of patients with mCRC who obtain greater benefit from ramucirumab.
Original languageEnglish
Pages (from-to)61-69
JournalEuropean Journal of Cancer
Volume78
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Carcinoembryonic antigen
  • CEA
  • Colorectal carcinoma
  • Metastatic
  • Phase III clinical trial
  • Predictive
  • Ramucirumab

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    Yoshino, T., Obermannová, R., Bodoky, G., Garcia-Carbonero, R., Ciuleanu, T., Portnoy, D. C., Kim, T. W., Hsu, Y., Ferry, D., Nasroulah, F., & Tabernero, J. (2017). Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial. European Journal of Cancer, 78, 61-69. https://doi.org/10.1016/j.ejca.2017.03.007