Rapid Review of Published Economic Evaluations of Larotrectinib and Entrectinib: Current Practices to Overcome Challenges in Health Technology Assessment of Tumor-Agnostic Treatments

OBJECTIVES: Tumor-agnostic treatments target cancer based on its genetic and molecular characteristics, regardless of the tumor's histology. This variability presents significant challenges for health technology assessment (HTA) agencies in evaluating these treatments. This study aimed to review the published economic evaluations of two tumor-agnostic therapies, larotrectinib and entrectinib, and to summarize existing practices for addressing the associated challenges.

METHODS: A rapid literature review adhering to PRISMA principles was conducted using PubMed, Embase, CEA Registry, PROSPERO, and Cochrane Library, covering all available records up to June 2024. The review included scientific articles and conference presentations evaluating the cost-effectiveness of larotrectinib and entrectinib in tumor-agnostic indications. General characteristics of the economic evaluations were extracted, and efforts to address challenges were carefully examined, with a specific focus on the heterogeneity caused by investigating multiple tumor types and limitations of clinical input data.

RESULTS: A total of 151 records were identified and screened by titles and abstracts. Of these, 14 proceeded to full-text screening, and 9 were considered relevant to this study. Six independent model-based economic analyses were identified, while the remaining three were country adaptations and updates of these models. Among the six primary analyses, three investigated entrectinib and three examined larotrectinib. Five analyses employed a partitioned survival approach, and one used microsimulation method. All models applied extrapolations over a lifetime horizon. To construct the comparator arm, three studies relied on literature data, one used real-world data, one utilized a non-responder control, and one analysis employed three different approaches in parallel. All analyses reported pooled cost per QALY for all tumors included, with only one study also calculating tumor-specific ICERs.

CONCLUSIONS: There is substantial heterogeneity in the published economic evaluation methods for assessing tumor-agnostic treatments. Based on the findings, utilizing multiple approaches in parallel is recommended to enhance the robustness of results and better support HTA decisions.