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Phase II Randomized Trial on Dose-Escalated Sorafenib vs Best Supportive Care (BSC) in Patients With Advanced Hepatocellular Carcinoma (HCC) With Disease.

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Presentation on theme: "Phase II Randomized Trial on Dose-Escalated Sorafenib vs Best Supportive Care (BSC) in Patients With Advanced Hepatocellular Carcinoma (HCC) With Disease."— Presentation transcript:

1 Phase II Randomized Trial on Dose-Escalated Sorafenib vs Best Supportive Care (BSC) in Patients With Advanced Hepatocellular Carcinoma (HCC) With Disease Progression on Prior Sorafenib Treatment Pressiani T 1, Rimassa L 1, Boni C 2, Labianca R 3, Fagiuoli S 3, Ardizzoni A 4, Foa P 5, Cortesi E 6, Porta C 7, Artioli F 8, Latini L 9, Carnaghi C 1, Lutman FR 1, Torzilli T 1, Tommasini MA 1, Cerianl R 1, Covini G 1, Giordano L 1, Locopo N 1, Santoro A 1. 1 Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano (MI), Italy; 2 Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 3 Ospedali Riuniti, Bergamo, Italy; 4 Azienda Ospedaliero - Universitaria, Parma, Italy; 5 Ospedale San Paolo - Polo Universitario, Milano, Italy; 6 Azienda Policlinico Umberto I, Roma, Italy; 7 I.R.C.C.S. Policlinico San Matteo, Pavia, Italy; 8 Ospedale B. Ramazzini, Carpi (MO), Italy; 9 Ospedale Generale Provinciale, Macerata, Italy.

2 Study Design Primary endpoint: PFS Sorafenib 600 mg BID 49 patients Advanced HCC Child-Pugh Class A/B Suitable for systemic treatment (300 patients) Sorafenib 400 mg BID PD BSC 52 patients Randomization 1:1 (101 patients) From April 2007 to July 2008, 300 patients were prospectively treated with sorafenib 400 mg BID. At documented radiological PD, 101 patients (34%) were randomized: 49 patients (48.5%) to increased-dose sorafenib (600 mg BID) + BSC and 52 patients (51.5%) to BSC, respectively PD=radiological progression, PFS=progression-free survival. Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

3 Baseline Patient Characteristics No. of Patients (%) Sorafenib no. (%) BSC no. (%) P value Total101 (100)49 (48.5)52 (51.5) Sex.089 Male83 (82.2)37 (75.5)46 (88.5) Female18 (17.8)12 (24.5)6 (11.5) Child-Pugh Class.113 A94 (93.1)48 (98.0)46 (88.5) B7 (6.9)1 (2.0)6 (11.5) Histological subtype*1.00 Trabecular80 (79.2)38 (97.4)42 (93.33) Mixed1 (1.0)0 (0.0)1 (2.22) Fibrolamellar3 (3.0)1 (2.6)2 (4.44) Missing17 (16.8) Extrahepatic spread*.035 Yes69 (68.31)38 (82.6)31 (63.3) No26 (25.74)8 (17.4)18 (36.7) Missing6 (5.94) Time at first relapse months49 (48.5)21 (42.9)28 (53.9) >4 months52 (51.5)28 (57.1)24 (46.2) Associations are tested using the Chi-square test. *The sum does not add up to the total due to missing values. Associations are tested using the Fisher exact test. Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

4 Progression-Free Survival HR sorafanib vs BSC, 0.67; CI 95%: ( ), Pvalue:.089 Risk reduction of 33% All Median (range)Sorafenib Median (range)BSC Median (range) PFS (months)3.58 ( )3.91 ( )2.69 ( ) CI=confidence interval, HR=hazard ratio. Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

5 Time to Progression HR sorafanib vs BSC, 0.59; CI 95%: ( ), Pvalue:.070 Risk reduction of 41% All Median (range)Sorafenib Median (range)BSC Median (range) TTP (months)3.64 ( )3.97 ( )2.0 ( ) TTP=time to progression. Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

6 Overall Survival (OS) HR sorafanib vs BSC, 0.71; CI 95% : ( ); Pvalue:.107 Risk reduction of 29% All Median (range)Sorafenib Median (range)BSC Median (range) TTP (months)6.11 ( )7.55 ( )5.89 ( ) Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

7 Adverse Events Adverse Events (Grade 3/4) Sorafenib No. (%) BSC No. (%) Pvalue Diarrhea9 (12.2)6 (11.5).335 Hand foot skin reaction5 (6.3)8 (15.4).437 Fatigue8 (16.3)4 (7.7).226 Rash3 (6.1)4 (7.7)1.000 Weight loss6 (12.2)1 (1.9).055 Anemia4 (8.1)1 (1.9).196 Stomatitis5 (6.3)0 (0.0).024 Cachexia3 (4.1)2 (3.8).672 Abdominal pain4 (8.1)0 (0.0).052 Nausea and vomiting2 (3.8)1 (1.9).610 Encephalopathy2 (3.8)0 (0.0).233 Amylase increase1 (2.0)1 (1.9)1.000 Thrombocytopenia1 (2.0)1 (1.9)1.000 Pain (non abdominal)1 (2.0)1 (1.9)1.000 Cardiovascular1 (2.0)1 (1.9)1.000 Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

8 Drug Exposure Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

9 All Patients (300): PFS and OS According to Child-Pugh Class Median (range) OSPFS All (months)9.2 ( )4.1 ( ) n=234 Child-Pugh Class A (months)10.9 ( )4.7 ( ) n=62 Child-Pugh Class B (months)4.0 ( )2.6 ( ) Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

10 Conclusions These results demonstrate that increased-dose sorafenib in HCC patients progressing on standard-dose sorafenib is feasible, with an acceptable safety profile. Trend toward improved PFS and OS, although not statistically significant, may justify the use of increased or standard dose of sorafenib beyond progression as an active control arm in Phase II – III trials evaluating new drugs as second-line therapy in HCC Adapted from Pressiani T et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.


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