OBJECTIVES: Adagrasib, a novel oral KRAS G12C inhibitor, demonstrated an objective response rate (ORR) of 42.9% in the KRYSTAL-1 Phase 2 trial, among patients with advanced/metastatic KRAS G12C-mutated NSCLC previously treated with chemoimmunotherapy (FDA approval in December-2022).

Sotorasib, another KRAS G12C inhibitor, demonstrated an ORR of 37.1% in the Phase 2 trial CodeBreaK100 (FDA approval in May-2021) and 28.1% in the Phase 3 randomized trial, CodeBreaK200.

No head-to-head clinical trials comparing adagrasib and sotorasib are available. A cost-effectiveness model was developed to compare expected cost per response between adagrasib and sotorasib.

METHODS: The ORRs and treatment-related adverse events (TRAEs) were adjusted for differences in baseline characteristics between KRYSTAL-1 and CodeBreaK200 using matching-adjusted indirect comparisons (MAICs). Sensitivity analysis using CodeBreaK100 was assessed. The analysis included only Grade ≥ 3 TRAEs occurring in ≥5% patients. Treatment-related direct medical costs were incorporated: drug acquisition, monitoring and TRAE management. Treatment costs for adagrasib and sotorasib were based on wholesale acquisition costs, median treatment duration times (5.7 and 4.6 months) and relative drug intensity (76.5 and 89.2%), as observed in clinical trials.

RESULTS: The MAIC increased the ORR odds ratio from 1.92 (95%CI 1.16-3.17) to 2.22 (95%CI 1.25-3.96). Adjusted ORR of adagrasib was higher than sotorasib (46.5% vs 28.1%). Treatment costs were comparable ($100,135 adagrasib; $102,502 sotorasib); main cost differentiators were drug acquisition and TRAE management costs (both favoring adagrasib). The cost to achieve one response was $215,451 for adagrasib and $364,774 for sotorasib, resulting in $149,323 saved per response achieved. The number needed to treat to achieve one additional response was 5.44, meaning one additional response is expected when treating 5 patients with adagrasib instead of sotorasib.

CONCLUSIONS: At a similar cost, adagrasib is a more effective and cost-efficient option compared to sotorasib for achieving ORR in patients with previously treated KRAS G12C-mutated NSCLC.