Second line systemic therapy options for advanced hepatocellular carcinoma; a systematic review

Abstract

This systematic review aims at evaluation of the level of evidence for the use of second-line systemic therapy for patients with hepatocellular carcinoma. Eligible studies were identified using database search. Eligible studies reported efficacy and/or toxicity data for patients with hepatocellular carcinoma receiving second-line systemic chemotherapy. Twenty five studies were eligible and were included in the final analysis. Median progression-free survival was reported in 20 out of the 25 studies and it ranged from 1.8 to 11 months. Median overall survival was reported in 18 out of 25 studies and it ranged from 6.6 months to 16 months. Reported grade 3/4 toxicities were regimen-specific and it includes hepatotoxicity, hypertension, and hematologic toxicities. However, positive results from the use of some agents need further confirmation in prospective studies

Keywords:

• hepatocellular carcinoma
• salvage treatment
• second line
• sorafenib
• systemic treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

Background

• The randomized Phase III SHARP trial provided level A evidence for first-line systemic treatment with sorafenib in advanced hepatocellular carcinoma (HCC).

• This systematic review aims at evaluation of the level of evidence for the use of second-line systemic therapy for patients with HCC in terms of OS, response and toxicity.

Methods

• Eligible studies were identified using MEDLINE, Google scholar, American society of clinical oncology, European society of medical oncology and the Cochrane databases.

• Searches were last updated on 1 June 2014. Eligible studies reported efficacy and/or toxicity data for patients with HCC receiving second-line systemic chemotherapy.

Results

• Four hundred and fifty one results were obtained from the searches in MEDLINE (n = 303 studies) and other databases (n = 148).

• Twenty-five studies (involving 1457 patients) were considered eligible and were included in the final analysis: two Phase III trials, 15 Phase II clinical trials, one Phase I trial and seven retrospective studies.

• Median PFS was reported in 20 out of the 25 studies, and it ranged from 1.8 to 11 months. Median OS was reported in 18 out of 25 studies and it ranged from 6.6 to 16 months. The DCR was reported in 18 studies, and it ranged from 30 to 75%.

• Reported grade 3/4 toxicities were regimen specific and it includes hepatotoxicity, hypertension, gastrointestinal toxicities, mucocutaneous toxicities and hematologic toxicities.