Real-world outcomes of patients with human epidermal growth factor 2 (HER2)–positive breast cancer receiving neoadjuvant therapy without adjuvant ado-trastuzumab emtansine (T-DM1).

Abstract

584 Background: HER2-positive early-stage breast cancer (EBC) treated with neoadjuvant chemotherapy and HER2-targeted therapy has favourable outcomes, especially for those attaining pathologic complete response (pCR). Among those with residual invasive disease (RD), outcomes are variable. Replacing adjuvant trastuzumab with ado-trastuzumab emtansine (T-DM1) reduces the risk of recurrence, but increases toxicity and cost. The magnitude of benefit of T-DM1 may be small among patients with RD and favourable prognostic features. Here we report on real-world outcomes of patients with HER2-positive EBC treated with neoadjuvant therapy without adjuvant T-DM1. Methods: We performed a single institution, retrospective review of HER2-positive EBC treated with neoadjuvant chemotherapy and trastuzumab between January 1st, 2012 and February 1, 2021. We excluded patients who received adjuvant T-DM1. We collected clinical and pathologic characteristics, treatment data, and outcomes events. We estimated 3-year disease-free survival (DFS), a validated endpoint in HER2-positive EBC, using Kaplan-Meier with recurrence and/or death as events. Outcomes were reported in subgroups based on known prognostic factors. The study was approved by the University Health Network Research Ethics Board. Results: The study comprised 193 patients with a median follow-up of 30 months. The majority (n=160, 83%) received neoadjuvant anthracycline and taxane-based chemotherapy; 42 (22%) received neoadjuvant pertuzumab. All received adjuvant trastuzumab. Median age was 53 years (range 25-87), 113 (59%) patients had estrogen receptor (ER) positive disease, and 82 (42%) had pCR. In total, 16 events were observed, of which 13 (81%) were distant recurrences (including 5 (31%) in the brain) and 3 (19%) were locoregional. Of these, 14 (88%) occurred in the first 3 years of follow-up. Estimated 3-year DFS was 98.6% in patients with pCR, and 85.4% in patients with RD. Patients with ER positive disease had excellent outcomes, regardless of pathologic nodal (ypN) status. The highest risk of recurrence was in ER negative and ypN positive disease (Table). Conclusions: Real-world outcomes of patients with HER2-positive EBC treated with neoadjuvant therapy without adjuvant T-DM1 are favorable, including those with RD if ER positive. The expected benefit of adjuvant T-DM1 in this group is therefore likely to be small. Patients with ER- disease had poorer outcomes irrespective of nodal status. Further research to identify patients with RD for whom the benefit of T-DM1 is unlikely to merit its added toxicity and cost is warranted. [Table: see text]