Dataset Information

Sorafenib alone vs. sorafenib plus GEMOX as 1^st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

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.

SUBMITTER: Assenat E

PROVIDER: S-EPMC6734663 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sorafenib alone vs. sorafenib plus GEMOX as 1<sup>st</sup>-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Assenat Eric E Pageaux Georges-Philippe GP Thézenas Simon S Peron Jean-Marie JM Bécouarn Yves Y Seitz Jean-François JF Merle Philippe P Blanc Jean-Frédéric JF Bouché Olivier O Ramdani Mohamed M Poujol Sylvain S de Forges Hélène H Ychou Marc M Boige Valérie V

British journal of cancer 20190404 9

<h4>Background</h4>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.<h4>Methods</h4>Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m<sup>2</sup> gemcitabine; 100 mg/m<sup>2</sup> oxaliplatin). Primary endpoint was the 4-month progressio ...[more]

PMID: 30944458

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Project description:ImportancePrevious communication has reported significant improvement in overall survival (OS) when using doxorubicin plus sorafenib in the treatment of advanced hepatocellular cancer (HCC).ObjectiveTo determine if doxorubicin added to sorafenib therapy improves OS, with stratification for locally advanced and metastatic disease.Design, setting, and participantsThis unblinded randomized phase 3 clinical trial was led by Alliance in collaboration with Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Canadian Cancer Trials Group, and Southwest Oncology Group. It was launched in February 2010 and completed in May 2015; data were also analyzed during this time frame. Patients with histologically proven advanced HCC, no prior systemic therapy, Child-Pugh grade A score, Eastern Cooperative Oncology Group performance status of 0 to 2 (later amended to 0-1), and adequate hematologic, hepatic, renal, and cardiac function were eligible. The OS primary end point had a final analysis planned with 364 events observed among 480 total patients with 90% power to detect a 37% increase in median OS.Interventions or exposuresPatients received either 60 mg/m2 of doxorubicin every 21 days plus 400 mg of sorafenib orally twice daily or the sorafenib alone, adjusted to half doses for patients with bilirubin levels of 1.3 to 3.0 mg/dL.Main outcomes and measuresThe primary end point was OS, and progression-free survival (PFS) was a secondary end point.ResultsOf 356 patients included in the study, the mean (SD) age was 62 (10.1) years, and 306 (86.0%) were men. Although it was planned to include 480 patients, the study was halted after accrual of 356 patients (180 patients treated with doxorubicin plus sorafenib and 176 with sorafenib alone) with a futility boundary crossed at a planned interim analysis. Median OS was 9.3 months (95% CI, 7.3-10.8 months) in the doxorubicin plus sorafenib arm and 9.4 months (95% CI, 7.3-12.9 months) in the sorafenib alone arm (hazard ratio, 1.05; 95% CI, 0.83-1.31). The median PFS was 4.0 months (95% CI, 3.4-4.9 months) in the doxorubicin plus sorafenib arm and 3.7 months (95% CI, 2.9-4.5 months) in the sorafenib alone arm (hazard ratio, 0.93; 95% CI, 0.75-1.16). Grade 3 or 4 neutropenia and thrombocytopenia adverse events occurred in 61 (36.8%) and 29 (17.5%) patients, respectively, being treated with doxorubicin plus sorafenib vs 1 (0.6%) and 4 (2.4%) patients treated with sorafenib.Conclusions and relevanceThis multigroup study of the addition of doxorubicin to sorafenib therapy did not show improvement of OS or PFS in patients with HCC.Trial registrationClinicalTrials.gov identifier: NCT01015833.

Project description:ImportanceSorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study.ObjectiveTo investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion.Design, setting, and participantsThis randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months.InterventionsRandomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks).Main outcomes and measuresThe primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.ResultsFor 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]).Conclusions and relevanceSorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion.Trial registrationClinicalTrials.gov identifier: NCT02774187.

Project description:Background & aimsPortal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis.MethodsRegistered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events.ResultsBetween May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events.ConclusionsConcurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis.Impact and implicationsTreatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis.Clinical trials registrationThis study is registered at ClinicalTrials.gov (NCT03535259).

Dataset Information

Sorafenib alone vs. sorafenib plus GEMOX as 1^st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Background

Methods

Results

Conclusions

Publications

Sorafenib alone vs. sorafenib plus GEMOX as 1<sup>st</sup>-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Sorafenib alone vs. sorafenib plus GEMOX as 1st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Background

Methods

Results

Conclusions

Publications

Sorafenib alone vs. sorafenib plus GEMOX as 1<sup>st</sup>-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Sorafenib alone vs. sorafenib plus GEMOX as 1^st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial.