Authors' objectives: To assess the effectiveness, safety and economic implication of first line targeted therapy for advanced hepatocellular carcinoma to be used in routine clinical practice in Ministry of Health (MOH) facilities.

Authors' results and conclusions: There was sufficient fair to good level of evidence retrieved on first line targeted therapy for advanced hepatocellular carcinoma. In terms of effectiveness, evidence showed the combination of atezolizumab with bevacizumab was significantly longer overall survival, progression-free survival and objective response rate as compared with sorafenib. While lenvatinib showed improved progression-free survival, time to progression as well as objective response rate. Our pooled meta-analysis showed that adverse events were significantly higher on decreased appetite, proteinuria, dysphonia, weight loss and hypothyroidism in patients treated with lenvatinib. The common grade III & IV adverse events related with atezolizumab-bevacizumab was hypertension, proteinuria, increased of AST and ALT. Moreover, while lenvatinib and combination of atezolizumab with bevacizumab were found to be a cost-effective option compared to sorafenib in other countries, it may not be the case in Malaysia due to the drug cost as well as difference in willingness-to-pay threshold per QALY gain.

Authors' recommendations: Based on the review, the combination of atezolizumab with bevacizumab showed slight improvement on survival, however due to the high cost and minimal gain, lenvatinib or sorafenib may be used as the first line treatment for selected patients. Due to the high cost associated with these targeted therapies, patient selection guide might be helpful in ensuring patients with high probabilities of benefiting from this type of treatment will have access to it despite budget constraint.

Authors' methods: Electronic databases were searched through the Ovid interface: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions(R)-1946 to January 31, 2022. PubMed and Google Scholar were used to search for additional literatures from the references of the retrieved articles. No limits were applied. The last search was conducted on 22nd April 2022.

Authors' identified further research: Treatment with PDL-1 was still evidence-limited, hence, we need more evidence to ensure the short term and long term effectiveness and safety.

Project Status: Completed

Year Published: 2022

URL for published report: https://www.moh.gov.my/index.php/database_stores/store_view_page/30/386

Requestor: Decision-making committee

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Malaysia

Organisation Name: Malaysian Health Technology Assessment

Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229

Contact Name: htamalaysia@moh.gov.my

Contact Email: htamalaysia@moh.gov.my

Copyright: Malaysian Health Technology Assessment Section (MaHTAS)