Simulation of Chemotherapy Effects in Older Breast Cancer Patients With High Recurrence Scores
A partir d'un modèle de simulation, cette étude estime l'intérêt, du point de vue de la réduction de la mortalité, d'ajouter une chimiothérapie adjuvante à un traitement endocrinien chez les patientes atteintes d'un cancer du sein HR+ HER2- de stade précoce et à haut risque de récidive, en fonction de 4 catégories d'âge (65-69 ans, 70-74 ans, 75-79 ans, 80-89 ans) et du niveau de comorbidité
Background : Tumor genomic expression profile (GEP) data is used to guide chemotherapy choice, but there are gaps in evidence for women 65+. We estimate chemotherapy effects by age and comorbidity-level among women with early stage, hormone-receptor+/HER2- breast cancers and Oncotype DX scores of 26+. Methods : A discrete-time stochastic state-transition simulation model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups based on age (65-69, 70-74, 75-79, 80-89y) and comorbidity-levels (no/low, moderate, severe). Outcomes were discounted at 3%, and included quality-adjusted life years (QALYs), life years, and breast cancer and other-cause mortality with chemo-endocrine vs. endocrine therapy. Sensitivity analysis tested the impact of varying uncertain parameters. Results : Women ages 65-69y with no/low comorbidity gained 0.16 QALYs with chemo-endocrine and reduced breast cancer mortality from 34.8% to 29.7%, for an absolute difference of 5.1%; this benefit was associated with a 12.8% rate of grade 3/4 toxicity. Women ages 65-69y with no/low or moderate comorbidity levels, and women aged 70-74 with no/low comorbidity had small chemotherapy benefits. All women ages 75+ experienced net losses in QALYs with chemo-endocrine therapy. The results were robust in sensitivity analyses. Chemotherapy had greater benefits as treatment effectiveness increased, but toxicity reduced the QALYs gained. Conclusion : Among women ages 65-89 whose tumors indicate a high recurrence risk, only those age 65-74y with no/low or moderate comorbidity have small benefits from adding chemotherapy to endocrine therapy. GEP testing (and chemotherapy use) should be reserved for women under age 75y without severe comorbidity.