Advances in the understanding of the molecular biology of endometrial cancer have led to the incorporation of several targeted therapies into standard treatment paradigms [[1], [2], [3], [4]]. Patients with mismatch repair-deficient (dMMR) tumors and microsatellite instability (MSI) have demonstrated responses to immune checkpoint inhibitors, such as dostarlimab and pembrolizumab [1,2]. Similarly, the monoclonal antibody trastuzumab has demonstrated efficacy in patients with human epidermal growth factor receptor type 2 (HER2)–overexpressing tumors, including 30–40 % of uterine serous cancers [3,4]. Recent clinical trials have demonstrated that the addition of these therapies to standard chemotherapy regimens can improve both progression-free (PFS) and overall survival (OS) [[1], [2], [3], [4]]. Trastuzumab is recommended by the National Comprehensive Cancer Network (NCCN) in combination with chemotherapy for frontline treatment of HER2-positive advanced-stage serous carcinomas and carcinosarcomas [5]. Pembrolizumab and dostarlimab combined with chemotherapy are each FDA-approved for first-line treatment of advanced-stage or recurrent endometrial cancer irrespective of mismatch-repair status, highlighting the growing role of immune checkpoint inhibitors in the treatment landscape [6,7].

Despite the proven efficacy of available frontline targeted therapies for advanced-stage endometrial cancer, each is associated with additional toxicities and cost. Novel biological therapies cost over $10,000 per cycle, are usually administered as “maintenance therapy” for several years after completion of chemotherapy, and may be FDA-approved in a “one-size-fits-all” fashion despite the ability to select the patients most likely to benefit based on biomarker testing. Considering the high cost of these drugs, the universal treatment of patients with targeted therapies regardless of tumor biomarker status is concerning. Prior cost-effectiveness studies addressing the use of immunotherapy for primary treatment of endometrial cancer have used variable methods and had conflicting results [[8], [9], [10], [11], [12]]. The cost-effectiveness of targeted therapies may vary by race/ethnicity based on the higher proportion of serous carcinomas and carcinosarcomas among Black patients; these malignancies are less commonly dMMR and more commonly HER2-overexpressing. Given the demonstrated benefits of targeted immunotherapy and HER2-directed therapies, we aimed to compare the cost, survival, and cost-effectiveness of biomarker-based and universal treatment strategies for newly diagnosed advanced-stage endometrial cancer in a US population, with specific and separate assessments for non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients.