Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study

OBJECTIVES Assessing the value of tumor-agnostic therapies (TAD) is challenging given the potential variability in treatment effects, trials with small sample sizes, different standards-of-care (SoC), and lack of comparative data from single-arm basket trials. Our study developed and applied novel methods to assess the value of pembrolizumab compared to SoC to inform coverage decisions. METHODS We developed a partitioned survival model to evaluate the cost-utility of pembrolizumab for previously treated patients with 8 advanced or metastatic MSI-H/dMMR cancers from a U.S. commercial payer perspective. Efficacy of pembrolizumab was based on data from trials directly or with adjustment using Bayesian hierarchical models (BHM). Eight chemotherapy-based external control arms were constructed from the TriNetX electronic health record databases. Tumor-specific health-state utility values were applied. All costs were adjusted to 2022 U.S. dollars. RESULTS At a lifetime horizon, pembrolizumab was associated with increased effectiveness compared to chemotherapies in colorectal (QALYs: +0.64, LYs: +0.64), endometrial (QALYs: +3.79, LYs: +5.47), and small intestine cancers (QALYs: +1.73, LYs: +2.48), but not for patients with metastatic gastric, cholangiocarcinoma, pancreatic, ovarian, and brain cancers. Incremental cost-effectiveness ratios (ICER) varied substantially across tumor types. Pembrolizumab was found to be cost-effective in treating colorectal and endometrial cancers (ICER: $121,967 and $139,257, respectively), and not cost-effective for other assessed cancers at a $150,000 willingness-to-pay/QALY threshold, compared to SoC chemotherapies. CONCLUSIONS The cost-effectiveness of TADs can vary by cancers. Using analytic tools such as external controls and BHMs can tackle several challenges in assessing the value of TADs and uncertainties from basket trials.