(316) Cost-effectiveness of sotorasib vs. adagrasib in KRAS G12C-mutated previously treated non-small cell lung cancer (NSCLC): An economic evaluation on Phase 3 trial results

Background: : Sotorasib and adagrasib are the only KRAS G12C inhibitors approved in the United States (US) for previously treated non-small cell lung cancer (NSCLC). Past economic evaluations relied on Phase 2 data and indirect comparisons. This study presents the first cost-effectiveness analysis (CEA) using Phase 3 evidence via matching-adjusted indirect comparison (MAIC) of the CodeBreaK 200 and KRYSTAL-12 trials to assess comparative efficacy and safety.

Objective: : To evaluate the cost-effectiveness of sotorasib versus adagrasib in previously treated KRAS G12C-mutated advanced NSCLC, from a US third-party payor perspective using Phase 3 data.

Methods: : A partitioned survival model was developed with a 20-year horizon, weekly cycle length, and a 1.5% annual discount rate. Progression-free survival (PFS) and overall survival (OS) for the sotorasib arm were modeled using parametric curves fitted to individual patient data from CodeBreaK 200. In the absence of mature OS data from KRYSTAL-12 and no significant PFS differences in the Phase 3 MAIC (HR=0.93; 95% CI: 0.70-1.22), equivalent efficacy was assumed. Adverse event (AE) rates were derived from the MAIC, which showed a consistently lower incidence of treatment-related AEs with sotorasib. Utilities were sourced from CodeBreaK 200 and adjusted for Grade 3–4 disutilities. Costs included drug acquisition, AE management, concomitant medications, KRAS G12C testing and terminal care. Probabilistic sensitivity analysis (PSA) assessed uncertainty.

Results: : Sotorasib was associated with comparable health outcomes (incremental QALYs: 0.0002) and lower total costs, yielding savings of $18,004 per patient compared with adagrasib. Cost differences were mainly driven by lower acquisition and AE management costs for sotorasib. AE incidence was lower across multiple categories, notably diarrhea (OR=0.50), nausea (OR=0.43) and vomiting (OR=0.11). Sotorasib was also associated with fewer dose reductions and interruptions compared to adagrasib, indicating a potentially lower management burden for care teams. At a $150,000/QALY willingness-to-pay threshold the net monetary benefit of sotorasib was $18,031. PSA showed a 62.0% probability of cost-effectiveness at this threshold.

Conclusions: : This Phase 3-informed analysis suggests sotorasib offers similar clinical outcomes to adagrasib with better safety and reduced overall costs, supporting its value as a cost-effective treatment option for previously treated KRAS G12C-mutated advanced NSCLC in the US.

Sponsorship:: Amgen Inc.