Real-word incidence and management of durable complete response in de novo metastatic HER2-positive breast cancer.

Abstract

e13017 Background: HER2-directed therapies enable a small number of patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long term durable responses (DR). However, clinic-pathologic factors that correlate with DRs in de novo HER2+ MBC are unknown. Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice, especially the effect on cardiotoxicity, are lacking in the literature. Methods: This is a retrospective case control study of patients with de novo HER2+ MBC who received treatment with trastuzumab at two NCI designated cancer centers between the years 2012-2017. Patients were included if ≥2 years of follow up data were available or if patients were deceased. DRs are defined as radiographic complete or partial response without progression or death at any point after diagnosis. Controls are patients with evidence of radiographic progression or death any point after diagnosis. Age at diagnosis, ER/PR status, site of metastasis, and initial treatment were analyzed. An un-paired T test for age and fisher exact test for categorical variables were used. Results: A total of 96 patients with de novo HER2+ MBC, 28 with DRs and 68 with progression, were identified. Average follow up length for patients with DR was 90 months (range 27-224 months). Patients who progressed had a mPFS of 17.5 months and a mOS of 60 months. Results are shown in Table. Additionally, six patients (6.3%) developed reduced ejection fraction, one with DR, five with progression. Nine patients have been receiving trastuzumab for over ten years with no evidence of disease. Only one patient opted to discontinue this therapy a year after complete response and is disease free five years from diagnosis. Conclusions: Nearly a third of patients with de novo metastatic HER2+ MBC in our dataset achieved DR. Factors that predict DRs include single organ involved by metastatic disease and more intensive upfront chemotherapy including trastuzumab and pertuzumab. The majority of patients with DR continued HER2 directed therapy indefinitely with minimal cardiotoxicity. In the absence of predictive biomarkers of DRs, indefinite trastuzumab administration is common practice for these patients. [Table: see text]