e23078 Background: KRAS G12C inhibitors have demonstrated efficacy in clinical trials for KRAS G12C–mutated non–small cell lung cancer (NSCLC), but U. S. real-world evidence on treatment durability, safety signals, healthcare utilization, and costs remains limited. Methods: We conducted a retrospective cohort study using the Highmark insurance claims database to evaluate adults with KRAS G12C–mutated NSCLC treated with sotorasib and/or adagrasib. Outcomes included treatment duration, time to treatment discontinuation (TTD; a claims-based durability metric used as a pragmatic surrogate for progression-free survival in the absence of radiographic data), adverse-event–related claims, emergency department (ED) visits, healthcare utilization, and total and per-patient-per-month (PMPM) costs during baseline versus follow-up. Medication costs for KRAS G12C inhibitors were estimated using CMS-imputed pricing to mitigate disclosure of negotiated rates and ensure analytic stability given the small sample size. Overall survival (OS) was estimated using Kaplan–Meier methods, and Cox proportional hazards models evaluated associations between time from diagnosis to KRAS G12C inhibitor initiation and OS. Results: The cohort included 53 patients with a median age of 67 years (IQR 62–73) ; 64% were female. Age was independently associated with worse OS (HR 1. 12 per year, 95% CI 1. 04–1. 20; p = 0. 003). Median treatment duration was 97 days (IQR 25–300). Median total costs increased from 121, 055 at baseline to 141, 843 during follow-up, with PMPM costs rising from 20, 176 to 21, 272. Adverse-event–related claims occurred in 40% of patients. Median TTD was 97 days overall and varied by treatment strategy, with the longest durability observed among patients receiving sequential KRAS G12C inhibitors (median 210 days, IQR 165–390). Conclusions: In this U. S. claims analysis, KRAS G12C inhibitor therapy was associated with short real-world treatment durability (median TTD ~3. 2 months) and substantial PMPM costs (~21K), underscoring the economic impact of these agents in routine practice. Estimated survival probabilities were 16. 7% at 1 year and 5. 6% at 2 years from treatment initiation, lower than those reported in pivotal trials, suggesting a potential effectiveness–value gap in real-world care. Limitations include retrospective claims-based ascertainment, lack of radiographic progression data, small sample size, absence of a control group, and residual confounding.
Ramanan et al. (Thu,) studied this question.