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Clinical Trial
, 120 (9), 896-902

Sorafenib Alone vs. Sorafenib Plus GEMOX as 1 st-line Treatment for Advanced HCC: The Phase II Randomised PRODIGE 10 Trial

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Clinical Trial

Sorafenib Alone vs. Sorafenib Plus GEMOX as 1 st-line Treatment for Advanced HCC: The Phase II Randomised PRODIGE 10 Trial

Eric Assenat et al. Br J Cancer.

Abstract

Background: Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients.

Methods: Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m2 gemcitabine; 100 mg/m2 oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate.

Results: Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18).

Conclusions: Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.

Conflict of interest statement

E.A. reports personal fees from Bayer, Sirtex, Novartis, Ipsen and Sanofi, and travel and expenses from Bayer and Ipsen, outside the submitted work. P.M. reports personal fees from Bayer outside the submitted work. J.F.B. reports personal fees from Bayer, outside the submitted work. O.B. reports personal fees (board and speaker) from Amgen, Roche, Merck Sereno, Bayer, and from Pierre Fabre, Novartis and Lilly, outside the submitted work. All other authors have nothing to disclose regarding the present study.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram of the study
Fig. 2
Fig. 2
Progression-free survival (a) and time-to-progression (b) according to the treatment arm

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