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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 T1, Rimassa L1, Boni C2, Labianca R3, Fagiuoli S3, Ardizzoni A4, Foa P5, Cortesi E6, Porta C7, Artioli F8, Latini L9, Carnaghi C1, Lutman FR1, Torzilli T1, Tommasini MA1, Cerianl R1, Covini G1, Giordano L1, Locopo N1, Santoro A1. 1Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano (MI), Italy; 2Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 3Ospedali Riuniti, Bergamo, Italy; 4Azienda Ospedaliero - Universitaria, Parma, Italy; 5Ospedale San Paolo - Polo Universitario, Milano, Italy;6Azienda Policlinico Umberto I, Roma, Italy; 7I.R.C.C.S. Policlinico San Matteo, Pavia, Italy; 8Ospedale B. Ramazzini, Carpi (MO), Italy; 9Ospedale Generale Provinciale, Macerata, Italy. 1

2 Study Design Primary endpoint: PFS Advanced HCC
Child-Pugh Class A/B Suitable for systemic treatment (300 patients) Sorafenib 600 mg BID 49 patients Randomization 1:1 (101 patients) Sorafenib 400 mg BID PD BSC 52 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 Total 101 (100) 49 (48.5) 52 (51.5) Sex .089 Male 83 (82.2) 37 (75.5) 46 (88.5) Female 18 (17.8) 12 (24.5) 6 (11.5) Child-Pugh Class .113† A 94 (93.1) 48 (98.0) B 7 (6.9) 1 (2.0) Histological subtype* 1.00† Trabecular 80 (79.2) 38 (97.4) 42 (93.33) Mixed 1 (1.0) 0 (0.0) 1 (2.22) Fibrolamellar 3 (3.0) 1 (2.6) 2 (4.44) Missing 17 (16.8) Extrahepatic spread* .035 Yes 69 (68.31) 38 (82.6) 31 (63.3) No 26 (25.74) 8 (17.4) 18 (36.7) 6 (5.94) Time at first relapse .269 ≤4 months 21 (42.9) 28 (53.9) >4 months 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 TTP=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
Pvalue Diarrhea 9 (12.2) 6 (11.5) .335 Hand foot skin reaction 5 (6.3) 8 (15.4) .437 Fatigue 8 (16.3) 4 (7.7) .226 Rash 3 (6.1) 1.000 Weight loss 6 (12.2) 1 (1.9) .055 Anemia 4 (8.1) .196 Stomatitis 0 (0.0) .024 Cachexia 3 (4.1) 2 (3.8) .672 Abdominal pain .052 Nausea and vomiting .610 Encephalopathy .233 Amylase increase 1 (2.0) Thrombocytopenia Pain (non abdominal) Cardiovascular 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) OS PFS 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. 10 10 10


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