Real-world post-APT trial adoption of de-escalated systemic therapy and outcomes in small HER2-positive breast cancer: An NCDB analysis.

Abstract

539 Background: The APT trial shifted adjuvant management of small HER2-positive breast cancer towards paclitaxel-trastuzumab, yet real-world uptake and outcomes of de-escalated single-agent chemotherapy (SC) plus anti-HER2 therapy (H) vs multi-agent chemotherapy (MC) plus H remain uncertain. Methods: Using NCDB (2013-2022), we identified patients with invasive HER2-positive pT1a-pT1c, pN0/N1mi, M0 disease treated with surgery without neoadjuvant therapy. We compared treatment patterns pre-APT (2013-2014) vs post-APT (2016-2022), excluding 2015 as a washout. Regimens were grouped as local therapy only, H only, chemo only, SC + H, or MC + H. Predictors of SC + H were assessed with multivariable logistic regression in post-APT chemo + H recipients. OS was evaluated using time-varying Cox models (time zero surgery; treatment exposure starting at recorded systemic therapy initiation), adjusted for demographic, tumor, and facility factors. In the overall cohort, each regimen (H only, chemo only, SC+H, and MC+H) was compared with local therapy only. For pT1a tumors, comparisons were limited to H only, chemo only, and any chemo + H vs local therapy. To evaluate whether de-escalation was associated with similar OS, SC + H vs MC + H was compared in separate Cox models restricted to chemo + H recipients in pT1b and pT1c. Results: Among 56,455 patients, SC + H use increased from 12.5% pre-APT to 40.3% post-APT, while MC + H decreased from 46.6% to 24.8% ( p < 0.001). In the post-APT era among chemo + H recipients (N = 24,867), SC + H use increased with age (per 10-year OR 1.32, 95% CI 1.27-1.36) and hormone receptor-positive (HR-positive) status (OR 1.37, 95% CI 1.27-1.49), and less common with pT1c (OR 0.47, 95% CI 0.43-0.51) and N1mi (OR 0.21, 95% CI 0.17-0.24) tumors. In OS analyses of the entire cohort with available systemic start dates (N = 51,078; deaths = 3,246), SC + H (HR 0.62, 95% CI 0.57-0.67) and MC + H (HR 0.63, 95% CI 0.58-0.68) were associated with improved OS vs local therapy only. Additional independent predictors of mortality included Black race, older age, and higher tumor burden (T1c and N1mi), while HR-positive was linked to better OS. In pT1a cohort (N = 10,212; deaths = 461), any chemo + H was associated with improved OS vs local therapy (HR 0.83, 95% CI 0.70-1.00, p = 0.049), while H only (HR 0.85, 95% CI 0.51-1.42) and chemo only (HR 1.14, 95% CI 0.74-1.74) were not. Among chemo + H recipients, OS was similar for SC + H vs MC + H in pT1b (HR 0.96, 95% CI 0.80-1.16) and pT1c (HR 1.09, 95% CI 0.97-1.24) cohorts. Conclusions: Since APT, real-world care has shifted towards de-escalated SC + H regimens. Among treated pT1b and pT1c patients, OS was similar with SC vs MC backbones, supporting the feasibility of de-escalation in selected patients. In pT1a disease, the OS association for chemo + H was marginal ( p = 0.049) and should be interpreted cautiously given non-random treatment selection and low event rates.