Lenvatinib Plus Pembrolizumab vs. Chemotherapy in Pretreated Patients With Advanced Endometrial Cancer: A Cost-Effectiveness Analysis.

Background: In the international, randomized, open-label, phase 3 study 309-KEYNOTE-775 trial, lenvatinib plus pembrolizumab (LP) showed improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in pretreated patients with advanced endometrial cancer. This study aimed to investigate whether LP is cost-effective compared with chemotherapy. Materials and Methods: The clinical data for this model was derived from the 309-KEYNOTE-775 trial. Costs and utilities were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced endometrial cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether LP is cost-effective in patients with mismatch repair-proficient (pMMR) disease. Results: Lenvatinib plus pembrolizumab provided an incremental 0.64 quality-adjusted life years (QALYs) with an incremental cost of $241,278.18, compared with chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $378,251.44/QALY, which exceeded the willingness to pay (WTP) threshold. While in the pMMR subgroup, the ICER increased to $413,256.68/QALY. The variance of the utility of PFS state, the cost of LP, and the utility of the progressive disease state were the most influential factors in the sensitivity analysis. Conclusion: Under the current WTP threshold, LP is not cost-effective compared with chemotherapy in pretreated patients with advanced endometrial cancer.

Margetuximab Versus Trastuzumab in Patients With Advanced Breast Cancer: A Cost-effectiveness Analysis.

BACKGROUND: In the international, randomized, open-label, phase III study SOPHIA trial, margetuximab plus chemotherapy showed improved progression-free survival (PFS), and overall survival (OS) compared with trastuzumab plus chemotherapy. This study aimed to investigate whether margetuximab plus chemotherapy is cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer. MATERIALS AND METHODS: The clinical data for this model was derived from the SOPHIA trial. Costs and utility were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced breast cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether margetuximab is cost-effective in CD16A-158F allele carriers. RESULTS: Margetuximab plus chemotherapy provided an incremental 0.04 QALYs with an incremental cost of $66,109.78, compared with the trastuzumab plus chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $1,486,442.35/QALY, which exceeded the willingness to pay (WTP) threshold. While in the CD16A-158F allele carriers subgroup, the ICER decreased to $592,669.73/QALY. The variance of the utility of PFS state, costs of margetuximab, and utility of progressive disease state were the most influential factors in the sensitivity analysis. CONCLUSION: Under current WTP threshold, margetuximab plus chemotherapy is not cost-effective compared with trastuzumab plus chemotherapy in pretreated patients with ERBB2-positive advanced breast cancer. Selecting CD16A-158F allele carriers might be a considerable option to optimize the cost-effectiveness of margetuximab.

Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors.

BACKGROUND: The INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors. METHOD: We used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient's lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses. RESULTS: The base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000. CONCLUSION: As the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

Cost-Effectiveness Analysis of First-Line Nivolumab Plus Cabozantinib for Advanced Renal Cell Carcinoma in the United States.

INTRODUCTION: Nivolumab plus cabozantinib improved progression-free survival and overall survival compared with sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC) according to CheckMate 9ER study. METHODS: A Markov model was developed to compare the costs and effectiveness of nivolumab plus cabozantinib with those of sunitinib in the first-line treatment of advanced RCC. Primary outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model uncertainty was assessed in univariable and probabilistic sensitivity analyses. RESULTS: The total cost per patient was $681,425 for nivolumab plus cabozantinib and $256,302 for sunitinib. The incremental QALY for nivolumab plus cabozantinib was 0.49 compared with sunitinib. The ICER for nivolumab plus cabozantinib was $863,720 per QALY gained versus sunitinib. The results remained robust in univariable and probabilistic sensitivity analyses. CONCLUSIONS: On the basis of a willingness-to-pay threshold of $150,000, nivolumab plus cabozantinib was not cost-effective under current drug pricing in the first-line treatment of advanced RCC from a US payer's perspective.

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumor: A Systematic Review.

Background: The introduction of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the clinical effectiveness of patients with locally advanced and/or metastatic gastrointestinal stromal tumors (GIST), and this systematic review was conducted aiming at the cost-effectiveness analysis of TKIs in GIST. Methods: A thorough literature search of online databases was performed, using appropriate terms such as "gastrointestinal stromal tumor or GIST," "cost-effectiveness," and "economic evaluation." Data extraction was conducted independently by two authors, and completeness of reporting and quality of the evaluation were assessed. The systematic review was conducted following the PRISMA statement. Results: Published between 2005 and 2020, 15 articles were incorporated into the systematic review. For advanced GIST, imatinib followed by sunitinib was considered cost-effective, and regorafenib was cost-effective compared with imatinib re-challenge therapy in the third-line treatment. For resectable GIST, 3-year adjuvant imatinib therapy represented a cost-effective treatment option. The precision medicine-assisted imatinib treatment was cost-effective compared with empirical treatment. Conclusion: Although identified studies varied in predicted costs and quality-adjusted life years, there was general agreement in study conclusions. More cost-effectiveness analysis should be conducted regarding more TKIs that have been approved for the treatment of GIST. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO: CRD42021225253.