Cost-Effectiveness Analysis of Treating Patients With NTRK-Positive Cancer With the Histology-Independent Therapy Entrectinib

Objectives: This study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients. Methods: The health economic model consisted of a decision tree reflecting the NTRK testing phase followed by a microsimulation model reflecting treatment with either entrectinib or SoC. Efficacy of entrectinib was based on data from basket trials, whereas historical data from NTRK-negative patients were corrected for the prognostic value of NTRK fusions to model Results: Testing (testing for NTRK fusions, with subsequent entrectinib treatment in NTRK-positive patients and SoC in NTRK-negative patients) had higher per-patient quality-adjusted life-years (QALYs) and costs than No testing (SoC for all patients), with a difference of 0.0043 and euro732, respectively. This corresponded to an incremental cost-effectiveness ratio (ICER) of euro169 957/QALY and, using a cost-effectiveness threshold of euro80 000/QALY, an incremental net monetary benefit of 2euro388. When excluding the costs of genetic testing for NTRK fusions, the ICER was reduced to euro36 290/QALY and the incremental net monetary benefit increased to euro188. Conclusions: When treatment requires the identification of a genetic marker, the associated costs and effects need to be accounted for. Because of the low prevalence of NTRK fusions, the number needed-to-test to identify patients eligible for entrectinib is large. Excluding the testing phase reduces the ICER substantially.

Automated summary

This study addresses the challenges of evaluating histology-independent treatments using entrectinib as an example. It evaluates the cost-effectiveness of testing all patients for NTRK fusions and treating positive cases with entrectinib, compared to no testing and standard care. The results show that testing and treatment have higher costs and effects.