Outcomes of patients with T1a,b N0 Her2-positive breast cancer treated with adjuvant trastuzumab in a prospective registry in Ontario, Canada.

Abstract

533 Background: Multiple randomized trials of chemo +/- tras in early stage, Her 2 positive BrCa demonstrated improvement in survival, but patients (pts) with T1a,b N0 disease were mostly excluded. Given the uncertainty of benefit in this group and the toxicities of chemo + tras, treatment in Ontario was funded for these patients conditional upon data collection for toxicity and survival endpoints. We report the outcomes for 483 patients enrolled in this Evidence Building Program (EBP). Methods: Between 2011 and 2018, 483 eligible pts with Her 2 pos disease and adequate cardiac function were treated with chemo + tras in the EBP. Cardiac toxicity, febrile neutropenia (FN), event-free (EFS), and overall survival (OS) were determined for this cohort from administrative datasets, and compared retrospectively to controls of similar stage selected from the Ontario Cancer Registry who did not receive tras and/or chemo. For the EBP cohort, clinicians also reported changes in left ventricular ejection fraction (LVEF). Results: Pt characteristics are shown in the Table. EBP patients had improved OS when compared to controls who received no chemo or tras. The 3-year OS in the EBP pts was 99.1%, versus 96.9% in the controls [adjusted HR 0.59 (95% CI 0.29-1.20)]. Patients receiving EBP tras had a significantly longer EFS than controls with or without chemo [adjusted HR 0.54 (0.36-0.83), p=0.005]. Use of chemo + tras in EBP pts was associated with an increased risk of clinical congestive heart disease (CHD) and febrile neutropenia (FN). About 3.5% of pts experienced CHD during treatment with chemo + tras. About 6% of pts had an absolute reduction of LVEF >10% or reached LVEF <50%. In an adjusted analysis, the risk of CHD was higher in older pts [HR 1.06 (1.03-1.08) per 1-yr increase in age, p<0.0001) and for pts who received anthracyclines [HR 5.00 (1.71-14.7). In a matched analysis, the crude frequency of FN during treatment was 20% in EBP pts vs. 3% among controls who did not receive chemo or tras (p<0.001). Conclusions: Analysis of the Ontario EBP for pts with, T1a,b N0 HER2 pos BrCa revealed that the prognosis is excellent and is improved with the use of chemo + tras. The safety profile was expected and tolerable, especially when non anthracycline chemo was used. These results led to a funding policy change where prospective data collection has been discontinued and chemo + tras is now routinely funded in this population. [Table: see text]