A decade of HER2-targeted therapy in older patients with invasive breast cancer at Institut Curie

Abstract

Background: Around 40% and 20% of breast cancers (BC) occur in women aged ≥ 65 and≥ 75 years respectively. Although HER2-targeted therapy has profoundly improved the management of HER2+ BC, literature is short of data for frail and elderly patients reflecting the poor representation of older patients in registration trials. Methods: We conducted a retrospective analysis of any stage HER2+ BC patients aged ≥65 years treated with a HER2-targeted therapy at Institut Curie between 2000 and 2012 to assess treatment feasibility. Baseline data were extracted from the institution database and patients' files were reviewed for treatment compliance and safety profile. Results: From 2000 to 2012, 261 and 76 patients received anti-HER2 treatment in adjuvant and metastatic setting respectively. In adjuvant setting (age distribution 65-69/70- 74/≥75: 109/85/67; median follow-up 65 months), the median duration of trastuzumab treatment was 12 months with an 80% completion rate (defined as>9 months of treatment) decreasing significantly ≥75 years (70%). Grade ≥ 3 cardiac toxicity occurred in 9.6% of patients, was reversible in 72% of cases, and multivariate analysis identified the following risk factors for cardiac events: history of thromboembolic disease, valvulopathy and performance status (PS) ≥2 [OR 6.3 (95% CI: 1.4-27.7), 25.6 (4-162.8) and 18.2 (1.1-304.3) respectively], but not age. In metastatic setting (age distribution 65-74/≥ 75: 41/35; median follow-up 27 months), median duration of HER2-targeted therapy was 22.8 months (0-109.2), with no impact of age. Trastuzumab and lapatinib (alone or in combination) were mostly prescribed, pertuzumab and T-DM1 representing <15% of cases depending on treatment line. Multivariate analysis identified the following factors for mortality: PS≥2, history of thromboembolic disease [OR 3 (95% CI: 1.1-8.1) and 3.3 (0.7-16.3) respectively], but not age. Conclusions: HER2-targeted therapy seems feasible in≥65 yrs patients in both adjuvant and metastatic setting. Cardiac toxicity occurs in 10-15% but is reversible in most cases. Chronological age does not seem to affect duration of anti-HER2 treatment nor cardiac toxicity.