Authors' objectives: (i) To assess the comparative effectiveness and safety of immune checkpoint inhibitors in treating PD-L1 positive patients with advanced and metastatic NSCLC (ii) To determine the economic, organisational, ethical and social implications of implementing immunotherapy treatment options for this specific population of patients in the Ministry of Health hospitals.

Authors' results and conclusions: The ICI-based treatment was associated with higher survival and health-related quality of life benefit compared to standard chemotherapy in PD-L1 positive advanced NSCLC population. The benefits were more prominent in high PD-L1 expression population. In first line setting, pembrolizumab-chemotherapy has the highest probability to be better treatment option for PD-L1 positive population with non-squamous histo-subtype. Atezolizumab-chemotherapy combination had the highest probability to be better treatment option for those with high PD-L1 expression advanced NSCLC squamous subtype. In pre-treated population, nivolumab monotherapy had demonstrated the highest probability to be better treatment compared to others. In term of safety, ICI monotherapy had better safety profile compared to ICI-chemotherapy combination and standard chemotherapy based on the occurrence of serious adverse events. Fatal adverse event in immunotherapy was mainly associated with non-infectious pneumonitis (immune-related adverse event). Evidence from economic evaluation studies tend to suggest that ICI-based treatment is likely to be cost-effective in high-income countries and countries with WTP of ≥ USD100,000. Results from the conducted cost-effectiveness study indicate that PD-1/PD-L1 checkpoint inhibitors are unlikely to be cost-effective first- and second-line treatment options for Malaysians suffering from advanced NSCLC, regardless of PD-L1 expression status.

Authors' recommendations: Based on current evidence, pembrolizumab either as monotherapy or in combination with chemotherapy should be offered as standard treatment for patients with high PD-L1 expression non-squamous advanced NSCLC in the first line setting. Competitive pricing strategy and provision of effective policies on high-cost drugs are crucial in meeting the treatment needs.

Authors' methods: A comprehensive search was conducted on the following databases without any restriction on publication language and publication status. The Ovid interface: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non- Indexed Citations and Daily 1946 to July 27, 2022; Cochrane Library 2022 - Cochrane Database of Systematic Reviews – Cochrane Central Register of Controlled Trials (CENTRAL). Searches were also run in PubMed. 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 29 July 2022. A cost-effectiveness study based on three-health states Markov model with three-week cycle and a lifetime horizon was constructed to estimate the ICER of PD-1/L1 inhibitors compared to conventional chemotherapy in the first- and second-line treatment settings for advanced metastatic NSCLC. Input on the treatment effects was drawn from the systematic review. Meanwhile, costs for drug acquisition and disease management were based on available local data. Health utility values for progression free and progressive disease states and other key parameters applied to the model were sourced from previously published studies.

Authors' identified further research: Evidence reported were mostly from network meta-analysis (indirect comparison). Further studies of head-to-head comparison of immune checkpoint inhibitors are needed.

Project Status: Completed

Year Published: 2022

URL for published report: https://www.moh.gov.my/moh/modules_resources/bookshelf/IMMUNOTHERAPY_FOR_PD-L1_POSITIVE_ADVANCED_INLAY_NON-SMALL_CELL_LUNG_CANCER-update121220231/index.html#page/1

Requestor: Ministry of health

English language abstract: An English language summary is available

Publication Type: Full 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)