Abstract
Research probing the clinical utility of immune checkpoint inhibitors (ICIs) supports the development of novel, efficacious approaches to treating colorectal cancer (CRC) patients without chemotherapy. Therapeutic innovations, however, need to be evaluated in light of real-world economic considerations. This study compared the cost-effectiveness of first-line dual-immunotherapies, single immunotherapy, and chemotherapies in the treatment of microsatellite-instability-high/mismatch repair deficient (MSI-H/dMMR) advanced CRC from the perspective of American healthcare systems. Individual patient data (IPD) from the KEYNOTE-177 and CheckMate-8HW trials were collected with IPDfromKM and used to develop a Markov model with a 30-year duration and three mutually exclusive health states, providing a framework for the evaluation of the cost-effectiveness of first-line nivolumab together with ipilimumab, pembrolizumab, and chemotherapy for treating MSI-H/dMMR advanced CRC. Primary outcomes consisted of total costs, life years (LYs), quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER) values, and incremental net-health benefits (INHB) at willingness-to-pay (WTP) thresholds of $100,000/QALY in the USA. Nivolumab plus ipilimumab ($482,416 [18.72 QALYs]) and pembrolizumab ($336,617 [12.21 QALYs]) increased cost (effectiveness) by $145,800 (5.30 QALYs) than chemotherapy ($374,728 [10.07 QALYs]), respectively. The corresponding ICER was $13,670/QALY and -$14,768/QALY, with INHB of 2.52 and 6.80 QALYs, respectively. It was further found that the ICER and INHB of nivolumab plus ipilimumab versus pembrolizumab were $22,386/QALY and 3.84 QALYs, respectively. In addition, the established model is stable. First-line immunotherapeutic treatments for MSI-H/dMMR advanced CRC cases in the USA appears to be cost-effective, with a dual-immunotherapeutic regimen consisting of nivolumab plus ipilimumab being preferable.