Authors' objectives: To assess the safety, effectiveness, cost-effectiveness and organisational issues of targeted therapies in combination with hormonal therapy as a first-line treatment for HR+, HER2-, metastatic breast cancer.

Authors' results and conclusions: A total of 986 records were identified through database and other sources. Fourteen studies were included in this review: three network meta-analysis, two systematic reviews with meta-analysis, one randomized control trial, six cost-effectiveness analyses, and two budget impact analysis. The evidence suggested that combination of CDK 4/6 inhibitors (palbociclib, ribociclib or abemaciclib) with AI resulted in longer PFS, higher overall response rate (ORR) and clinical benefit (CB) compared to AI monotherapy and fulvestrant-based therapies. When compared to chemotherapy agents, the combination treatment also showed improvement in PFS. Palbociclib, ribociclib and abemaciclib (in combination with AI) demonstrated similar efficacy as a first-line treatment for HR+, HER2-, metastatic breast cancer. In terms of safety, grade III or IV treatment-related side effects were significantly higher in patients who received combination treatment compared to AI monotherapy with commonly reported side effects of neutropaenia, leukopaenia, and anaemia. As for cost-effectiveness, ribociclib plus letrozole was a cost-effective therapy option compared to palbociclib plus letrozole. The estimated ICER varied across countries for both treatment options with different perspectives and thresholds

Authors' recommendations: Combination of CDK 4/6 inhibitors with AI is recommended as a first-line treatment for HR+, HER2-, metastatic breast cancer. Ribociclib plus letrozole might be a cost-effective options for this population.

Authors' methods: Electronic databases were searched through the Ovid interface: Ovid MEDLINE® In-process and other Non-indexed citations and Ovid MEDLINE® 1946 to present, EBM Reviews - Cochrane Central Register of Controlled Trials – October 2020, EBM Reviews - Cochrane Database of Systematic Reviews - 2005 to October 2020, EBM Reviews - Health Technology Assessment – 4th Quarter 2016, EBM Reviews – NHS Economic Evaluation Database 1st Quarter 2016. Google was used to search for additional web-based materials and information. Additional articles were identified from reviewing the references of retrieved articles. Last search was conducted on 2nd of November 2020.

Project Status: Completed

Year Published: 2020

URL for published report: http://www.moh.gov.my/index.php/database_stores/store_view_page/30/367

Requestor: Ministry of Health, 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)