Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial. (June 2017)

• Record Type: Journal Article
• Authors: Yoshino, Takayuki; Obermannová, Radka; Bodoky, György; Garcia-Carbonero, Rocio; Ciuleanu, Tudor; Portnoy, David C.; Kim, Tae Won; Hsu, Yanzhi; Ferry, David; Nasroulah, Federico; Tabernero, Josep
• Is Part Of: European journal of cancer. Volume 78(2017)
• Page Start: 61
• Page End: 69
• Publication Date: 2017-06
• Subjects: Metastatic -- Colorectal carcinoma -- Carcinoembryonic antigen -- CEA -- Predictive -- Ramucirumab -- Phase III clinical trial; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.03.007
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: Both high- and low-baseline CEA subgroups derive OS and PFS benefit from ramucirumab. Low-baseline CEA level may identify mCRC patients with greater ramucirumab response. That trend was observed across all RAISE trial randomisation strata. Elevated baseline CEA was a negative prognostic factor for PFS and OS in RAISE.