Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): Phase II, randomized, double-blind SPACE trial.

Cancers of the Pancreas Small Bowel and Hepatobiliary Tract
Session Type and Session Title: 
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


J Clin Oncol 30, 2012 (suppl 4; abstr LBA154^)
Riccardo Lencioni, Josep M. Llovet, Guohong Han, Won-Young Tak, Jiamei Yang, Marie-Aude Leberre, Woody Niu, Kate Nicholson, Gerold Meinhardt, Jordi Bruix; Division of Diagnostic Imaging and Intervention, Pisa University Hospital and School of Medicine, Pisa, Italy; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY; Xijing Hospital, Fourth Military Medical University, Shaanxi Province, China; Kyungpook National University Hospital, Daegu, South Korea; Eastern Hepatobiliary Hospital, Shanghai, China; Bayer Santé, Division of Bayer Schering Pharma, Loos, France; Bayer Healthcare Company, Beijing, China; Bayer Plc, Newbury, United Kingdom; Bayer HealthCare Pharmaceuticals, Montville, NJ; BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients (pts) with intermediate-stage HCC (BCLC B). Methods: Pts were eligible if they had asymptomatic, unresectable, multinodular tumors without vascular invasion (VI) or extrahepatic spread (EHS); Child-Pugh A liver functional status; and ECOG PS 0. Pts were randomized to receive S 400 mg bid or matching P continuously (1 cycle = 4 wks) until progression. All pts received TACE with DEBDOX (150 mg doxorubicin; Biocompatibles UK Ltd) 3-7d after first dose of study drug, and then on d1 (±4d) of months 3, 7, and 13, and q6 months thereafter. The primary endpoint was time to radiologic progression (TTP) by independent review (predefined alpha = 0.15). Secondary endpoints were overall survival (OS), time to VI/EHS, time to untreatable progression (TTUP), and safety. Results: Of 452 pts screened, 307 were randomized to S (n=154) or P (n=153). The HR for TTP was 0.797 (95% CI, 0.588, 1.080; p=0.072). Median TTP (50th percentile) was 169d/166d in the S and P groups, respectively; TTP at the 25th and 75th percentiles (preplanned) was 112/88d and 285/224d in the S and P groups, respectively. There were no unexpected safety findings. Median treatment duration in the S and P groups was 4.8 and 6.3 months, respectively, and median daily dose of study drug was 566 mg and 791 mg, respectively. Conclusions: The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX, compared with TACE with DEBDOX alone. The combination was well tolerated; no new safety findings that would preclude use of the combination were observed. The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE.

Assessment* TTP OS§ Time to VI/EHS§ TTUP

HR 0.797 0.898 0.621 1.586
95% CI 0.588, 1.080 0.606, 1.330 0.321, 1.200 1.200, 2.096
P value (1-sided) 0.072 0.295 0.076 0.999

* ITT population (all randomized pts); predefined alpha = 0.15; § median was not reached in either group.