Costs per avoided event (CPAE) in adjuvant CDK4/6 inhibitor therapy: A comparative analysis of subgroups from monarchE and NATALEE trials.

Abstract

e12542 Background: Assessing the economic efficiency of high-cost therapies like adjuvant CDK4/6 inhibitors for HR+/HER2- early breast cancer (EBC) is crucial. The Costs per avoided event (CPAE), based on the Number Needed to Treat (NNT), is a powerful metric indicating the investment required to prevent one disease recurrence. This study uses CPAE analysis to compare the economic efficiency across key subgroups from the monarchE (abemaciclib) and NATALEE (ribociclib) trials, aiming to inform value-based decision-making in Brazil. Methods: Invasive Disease-free Survival (iDFS) data (Hazard Ratio) for ITT and subgroups were derived from monarchE and NATALEE analyses. The NNT was calculated as the inverse of the Absolute Risk Reduction (1/ARR). monarchE enrolled: Cohort 1 (high-risk features) and Cohort 2 (Ki-67≥20%). NATALEE included a broader population, adding intermediate-risk patients. Treatment costs were based on 24 (abemaciclib) and 36 (ribociclib) cycles, using the factory price established by CMED (Brazil's drug regulation chamber) and applying an 18% ICMS tax rate. The CPAE for each subgroup was then calculated by multiplying its specific NNT by the total treatment cost. Results: Efficacy and economic metrics varied substantially across all analyzed subgroups, underscoring the critical impact of baseline risk on clinical and economic value (Table 1). In monarchE, the CPAE value was more favorable in high-risk subgroups, such as Cohort 1 with high Ki-67 (BRL 6.3MM), but escalated dramatically in the lower-risk, lower-benefit Cohort 2 (BRL 23.6MM). Similarly, in NATALEE, the CPAE was more favorable for higher-risk stage III patients (BRL 9.2MM) compared to stage II patients (BRL 13.8MM). These disparities demonstrate that the economic value of treatment is highly dependent on the baseline risk of the patient subgroup. Conclusions: Risk stratification can significantly optimize treatment costs and is a critical driver of cost-effectiveness. These findings underscore the importance of precise patient selection for the sustainable implementation of therapies in the Brazilian healthcare system. Clinical efficacy and economic efficiency of adjuvant CDK4/6 inhibitors for HR+/HER2- EBC. Study & Subgroup HR (iDFS) ARR (%) NNT CPAE (BRL MM) monarchE (ITT) 0.73 5% 20 10.5 monarchE (C1, Ki-67 high) 0.64 9% 12 6.3 monarchE (C2, Ki-67 high) 0.83 2% 45 23.6 NATALEE (ITT) 0.72 4.5% 23 11.3 NATALEE (Stage III) 0.70 5.6% 18 9.2 NATALEE (Stage II) 0.76 3.7% 27 13.8 NATALEE (N+) 0.71 4.4% 23 11.8 NATALEE (N0) 0.63 5.7% 18 9.2