Sotorasib More Cost-Effective in KRAS G12C NSCLC

Sotorasib is more cost-effective in treating patients with KRAS G12C non–small cell lung cancer (NSCLC) compared with adagrasib in second- and subsequent-line treatment, according to a new study.¹ This result can help clinicians choose the most appropriate treatment for their patient when addressing this form of NSCLC.

About 30% of lung adenocarcinoma cases in Western countries contain the KRAS gene mutation, with the G12C variant being the most common form and affecting 40% of those with a KRAS-mutated lung adenocarcinoma. In the US, KRAS G12C NSCLC has an estimated prevalence range of 8.9% to 19.0%.² Treatments for this specific type of NSCLC have been developed, including sotorasib and adagrasib, which may be equally effective based on previous studies. The present study used the matching-adjusted indirect comparison (MAIC) of phase 3 trial results to assess the cost-effectiveness of sotorasib compared with adagrasib in use as a second- and subsequent-line treatment for NSCLC.¹

The researchers used a partitioned survival model to perform this analysis. There were 3 health states included in the model: progression-free, progressed, and death. The model also used a cycle length of 1 week. Clinical and economic outcomes were projected over 20 years, with outcomes calculated as life-years, quality-adjusted life years (QALYs), and total costs (US$). The incremental cost-effectiveness ratio (ICER) was the primary outcome of the study.

Efficacy of the treatments was calculated using the progression-free survival (PFS) and overall survival (OS) data from the CodeBreaK 200 trial (NCT04303780). Incidence and economic burden of treatment-related adverse events were included in the model.

The researchers found that the total discounted costs were $18,004 higher for adagrasib compared with sotorasib in the base case of the treatments having equivalent efficacy. Sotorasib had a net monetary benefit of $18,031, making it more cost-effective at its base case. The mean incremental costs were $4321 lower in sotorasib, and there was a mean gain of 0.004 in QALYs. Sotorasib was also able to bring more health benefits and was more effective than adagrasib compared with the willingness-to-pay threshold. The ICER was not reported, as sotorasib was dominant in the base case.

Sotorasib had a higher probability of being more cost-effective at all willingness-to-pay thresholds compared with adagrasib, with a probability of 62.4% at a willingness-to-pay threshold of $150,000. This probability was maintained at thresholds of $100,000 and $200,000, with the probabilities being 61.0% and 61.6% in those respective instances.

There were some limitations to this study. The MAIC relies on all prognostic and effect-modifying variables being adjusted for. Some residual compounding may be possible despite covariate adjustment. The phase 3 KRYSTAL-12 trial (NCT04685135) had not been completed when the cost-effectiveness analysis was performed, which disallowed including mature OS data. Study populations from different studies were used for this analysis to extract data on the frequency of adverse events and costs, which could have affected results. Utility values were unavailable for adagrasib, and the values for sotorasib were used instead. Real-world PFS and OS were not available for adagrasib, which meant the analysis could not be evaluated against real-world findings.

The researchers concluded that “sotorasib and adagrasib have comparable efficacy based on currently available data, whereas sotorasib has a more favorable safety profile, which translates into a modest QALY gain, and a lower acquisition cost.” The researchers stated that sotorasib may be the preferred medication to use going forward.

References

1. Karim N, Waterhouse D, Jones S, Stollenwerk B. Cost-effectiveness of sotorasib versus adagrasib in previously treated KRAS G12C-mutated advanced NSCLC: a US healthcare payer perspective. J Med Econ. 2026;29(1):77-92. doi:10.1080/13696998.2025.2604968
2. Lim TKH, Skoulidis F, Kerr KM, et al. KRAS G12C in advanced NSCLC: prevalence, co-mutations, and testing. Lung Cancer. 2023;184:107293. doi:10.1016/j.lungcan.2023.107293