Sotorasib Demonstrates Cost-Effectiveness Over Adagrasib in Treating KRAS G12C-Mutated Lung Cancer
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A new study indicates that sotorasib is a more cost-effective treatment option for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) compared to adagrasib, particularly in second- and subsequent-line settings. The findings, published in the Journal of Medical Economics in July 2026, could significantly influence clinical decision-making for this challenging form of the disease.
Understanding KRAS G12C Mutations in Lung Cancer
Approximately 30% of lung adenocarcinoma cases in Western countries are driven by mutations in the KRAS gene. Within this group, the G12C variant is the most prevalent, affecting 40% of patients with a KRAS-mutated lung adenocarcinoma. In the United States, the estimated prevalence of KRAS G12C NSCLC ranges from 8.9% to 19.0%. The emergence of targeted therapies like sotorasib and adagrasib has offered new hope for patients with this specific genetic alteration.
Cost-Effectiveness Analysis: Sotorasib Takes the Lead
Researchers utilized a matching-adjusted indirect comparison (MAIC), analyzing phase 3 trial results to evaluate the economic impact of sotorasib versus adagrasib. The analysis, which modeled patient outcomes over a 20-year period, considered factors such as progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. A partitioned survival model was employed, categorizing patient health states as progression-free, progressed, or death, with weekly cycles used for projections. Outcomes were measured in life-years, quality-adjusted life years (QALYs), and total costs (in US dollars).
The study revealed that adagrasib incurred $18,004 higher total discounted costs compared to sotorasib, assuming equivalent efficacy. Sotorasib demonstrated a net monetary benefit of $18,031, indicating a more favorable economic profile. Mean incremental costs were $4321 lower with sotorasib, accompanied by a modest gain of 0.004 QALYs. “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,” one researcher stated.
Probability of Cost-Effectiveness
Sotorasib consistently showed a higher probability of being more cost-effective across various willingness-to-pay thresholds. At a threshold of $150,000, sotorasib had a 62.4% probability of being the more cost-effective option. This probability remained robust at $100,000 (61.0%) and $200,000 (61.6%). The incremental cost-effectiveness ratio (ICER) was not reported, as sotorasib was considered dominant in the base case analysis.
Study Limitations and Future Research
The researchers acknowledged several limitations. The MAIC method relies on accurate adjustment for all relevant variables, and residual confounding remains a possibility. Data from the phase 3 KRYSTAL-12 trial (NCT04685135) was not yet mature at the time of the analysis, preventing the inclusion of complete OS data. Furthermore, data on adverse event frequency and costs were sourced from different studies, potentially introducing variability. Utility values for adagrasib were unavailable, necessitating the use of sotorasib’s values instead. The absence of real-world PFS and OS data for adagrasib also limited the scope of the evaluation. .
Despite these limitations, the study provides compelling evidence supporting the cost-effectiveness of sotorasib. The researchers concluded that sotorasib may be the preferred medication for treating KRAS G12C-mutated NSCLC moving forward.
References:
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
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
