Cost-effectiveness of sotorasib versus adagrasib in previously treated KRAS G12C-mutated advanced NSCLC: a US healthcare payer perspective

To evaluate the cost-effectiveness of sotorasib versus adagrasib in the second- and later lines of treatment for KRAS G12C non-small cell lung cancer (NSCLC) from a US private payer perspective. A standard three-state partitioned survival model was used with a 20 year (life-time) horizon. Equivalent progression-free survival (PFS) and overall survival (OS) were assumed in the base case based on published matching-adjusted indirect comparisons (MAICs) of Phase 2 and 3 data, and time-to-death utilities applied. Treatment-related adverse events (TRAEs) common to both treatments were included. Direct costs and health benefits were discounted at 1.5% annually. Model robustness was explored through probabilistic sensitivity analysis (PSA) and inputs varied in scenario analyses. In the base case, sotorasib was more cost-effective than adagrasib, driven by lower acquisition cost and TRAE frequency. Total discounted costs were $18,004 higher for adagrasib than sotorasib ($246,557 vs $228,553), comprising: drug acquisition ($9,478), TRAE management ($4,103) and comedications (antiemetics and antidiarrheal agents; $4,424). Sotorasib was dominant at equivalent efficacy (1.20 quality-adjusted life-years [QALYs]). Net monetary benefit was $18,031 at a willingness-to-pay threshold (WTP) of $150,000/QALY. In the PSA, there was a higher probability of sotorasib being more cost-effective than adagrasib at all WTP thresholds (62% at a WTP of $150,000/QALY). Sotorasib was consistently more cost-effective than adagrasib in scenario analyses exploring relative efficacy, discount rate, time horizon, and utilities, with ICERs well below the $150,000/QALY WTP threshold. MAIC-based comparative effectiveness was used in the absence of head-to-head trial data; conclusions informed by MAIC should be interpreted with caution; long-term projections are limited without mature OS data; published data sources may be based on different populations. Sotorasib was more cost-effective than adagrasib in the second- and subsequent-line treatment of KRAS G12C NSCLC, based on current efficacy and safety data. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and is a leading cause of death from cancer. About 10% of patients with NSCLC have mutations in a particular part of the cancer-causing KRAS gene, known as the G12C variant. Sotorasib and adagrasib are used in the treatment of G12C-mutated NSCLC if chemotherapy has not worked well enough. This paper describes a cost-effectiveness model – a tool that can be used to compare how well treatments work, how much they cost, how often they cause adverse events (AEs), how much it costs to treat those AEs, and the effects on patients’ quality-of-life. Cost-effectiveness indicates the value of a treatment compared with its cost. This is useful when making decisions about treatments. A published paper has reported that sotorasib and adagrasib work similarly well to prolong the life of patients with G12C-mutated NSCLC. However, patients taking adagrasib had more AEs. This information was used in the model. Adagrasib costs more than sotorasib and is also associated with higher costs for managing AEs and for medicines to treat diarrhea and sickness/vomiting. The cost-effectiveness model showed that, overall, sotorasib provides better value for money to healthcare services in the USA. The information in the model was varied in different ways and different assumptions were made about how well the treatments work and their effect on quality-of-life. In most of these variations, sotorasib provided better value for money than adagrasib to healthcare services in the US.