BACKGROUND: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. METHODS: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. RESULTS: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). CONCLUSIONS: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.

Department of Experimental Diagnostic and Specialty Medicine University Hospital S Orsola 40138 Bologna Italy

Department of Gastroenterology and Digestive Oncology University Hospital of St Etienne 42100 Saint Etienne France

Department of Gastroenterology and Hepatology Kindai University Faculty of Medicine Osaka Sayama 589 8511 Japan

Department of Hepato Gastroenterology and Medical Oncology CHU de Bordeaux Hôpital Haut Lévêque 33604 Pessac France

Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital Tokyo 104 0045 Japan

Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 701 Taiwan

Department of Medical Oncology Instituto do Câncer do Estado de São Paulo São Paulo 01246 000 Brazil

Department of Medical Oncology Yonsei Cancer Center Yonsei University College of Medicine Seoul 03722 Korea

Department of Medicine Harvard Medical School Massachusetts General Hospital Boston MA 02114 USA

Department of Medicine Royal Marsden Hospital Sutton Surrey SM2 5PT UK

Department of Oncology Asan Medical Center University of Ulsan College of Medicine Seoul 05505 Korea

Department of Oncology Santa Maria del Prato Hospital Feltre 32032 Italy

Department of Oncology University Hospital Motol 2nd Faculty of Medicine of Charles University 150 00 Praha Czech Republic

Department of Surgery Graduate School of Medicine Kyoto University Kyoto 606 8507 Japan

Departmentof Surgery The University of Hong Kong Pokfulam Hong Kong

Division of Gastroenterology and Hepatology Department of Medicine Taipei Veterans General Hospital Taipei 112 Taiwan

Division of Hematology Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 135 710 Korea

Division of Hepatobiliary and Pancreatic Oncology Kanagawa Cancer Center Yokohama 241 0815 Japan

Eli Lilly and Company Indianapolis IN 46285 USA

Eli Lilly and Company New York NY 10016 USA

National Yang Ming University School of Medicine Taipei 112 Taiwan

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