Meta-analysis in HER2+ early breast cancer therapies and cost-effectiveness in a Brazilian perspective

Abstract

Background: HER2-targeted therapy was a paradigm shift for breast cancer. However, the optimal duration of adjuvant trastuzumab remain unknown. This issue is important in lower and middle-income countries such as Brazil where financial resources are scarce. The aim of this study is to determine which patients will benefit most with the addition of Pertuzumab to trastuzumab [T+P], trastuzumab for 12 months [T12] or trastuzumab for 6 months [T6]. Method(s): Individual data meta-analysis was performed using 5 studies (Persephone, Phare, Horg, Aphinity and Katherine) for the intention to treat (ITT) population. Through pooled analyzes of the Persephone, Phare and Horg studies, we compared 12 months and 6 months of trastuzumab. The comparison between T+P and T6 was performed through an indirect comparison using Bayesian methodology. For cost-effectiveness analysis, we compared the treatment lining up in pairs exclusively considering the data from the Aphinity (T+P vs T12), Persephone (T12 vs T6) and Katherine (T12 vs T-DM1), setting a 30 years period of time and costs of adjuvant treatments and after progression in the Brazilian perspective. Result(s): Individual data were analyzed from 12,753 patients. Patients who progressed in a 4-year period were 7.1% for T+ P, 10.2% for T12 (HR 1.37, 95% CI 1.16-1.63) and 12.9% for T6 (HR 1.73, 95% CI 1.45-2.06). Regarding DFS in the N+ subgroup, T+P showed HR 0.77 (95% CI 0.62-0.96) and 0.74 (95% CI 0.49-1.11) compared to T12 and T6, respectively. Among patients N-, T+P compared to T12 showed a HR 1.13 (95%CI 0.68-1.86) and compared to T6HR 0.83 (95%CI 0.45-1.52). ER+ patients, T+P showed HR 0.86 (95%CI 0.66-1.13) compared to T12 and HR 0.74 (95%CI 0.49-1.11) to T6. Among ER-, the values were HR 0.76 (95%CI 0.56-1.04) and HR 0.59 (95%CI 0.41-0.85), respectively. In the cost-effectiveness analysis, T+P demonstrated an ICER of $ 332,903 compared to T12, while T12 set side by side of T6 resulted in $ 42,774. In the subgroup N+, T+P presented $ 308,019 when compared to T12. T-DM1 was considered a cost-effective treatment with $ 3,031 compared to T12. Conclusion(s): The combination T+P presented an benefit in the subgroup N+, but it was not considered cost-effective. T6 may be considered a therapeutic option in low budget scenarios for patients HR+/N-.