Takayuki Yoshino1, Radka Obermannová2, György Bodoky3, Rocio Garcia-Carbonero4, Tudor Ciuleanu5, David C Portnoy6, Tae Won Kim7, Yanzhi Hsu8, David Ferry8, Federico Nasroulah9, Josep Tabernero10. 1. National Cancer Center Hospital East, Chiba, Japan. Electronic address: tyoshino@east.ncc.go.jp. 2. Masaryk Memorial Cancer Institute, Brno, Czech Republic. 3. St. László Hospital, Budapest, Hungary. 4. Hospital Universitario Doce de Octubre, CIBERONC, Madrid, Spain. 5. Institutul Oncologic Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania. 6. The West Clinic-University of Tennessee Health Sciences Center, Memphis, TN, USA. 7. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 8. Eli Lilly and Company, Bridgewater, NJ, USA. 9. Eli Lilly and Company, Buenos Aires, Argentina. 10. Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain.
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 failingbevacizumab- 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.
RCT Entities:
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.
Authors: Minkyu Jung; Min-Hee Ryu; Do Youn Oh; Myounghee Kang; Dae Young Zang; In Gyu Hwang; Keun-Wook Lee; Ki Hyang Kim; Byoung Yong Shim; Eun Kee Song; Sun Jin Sym; Hye Sook Han; Young Lee Park; Jin Soo Kim; Hyun Woo Lee; Moon Hee Lee; Dong-Hoe Koo; Hong Suk Song; Namsu Lee; Sung Hyun Yang; Dae Ro Choi; Young Seon Hong; Kyoung Eun Lee; Chi Hoon Maeng; Jin Ho Baek; Samyong Kim; Yeul Hong Kim; Sun Young Rha; Jae Yong Cho; Yoon-Koo Kang Journal: Gastric Cancer Date: 2018-02-09 Impact factor: 7.370
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