Background: Outcomes for breast cancer patients with residual disease (RD) after neoadjuvant chemotherapy (NACT) and HER2-targeted therapy may be better than anticipated leading to a smaller absolute benefit of adjuvant trastuzumab emtansine (T-DM1). Therefore, accurate estimates of 3-year disease-free survival (DFS) can aid in treatment planning.
Methods: We reviewed randomized trials of NACT and HER2-targeted therapy in breast cancer (excluding T-DM1) and calculated mean 3-year DFS weighted by study sample size. Meta-regression comprising linear regression weighted by sample size (mixed-effects) was performed to explore associations between 3-year DFS and year of accrual and trial-level patient, disease, and treatment factors. Data were reported quantitatively irrespective of statistical significance.
Results: Eleven studies (N = 3581) were included in the primary analysis. The mean 3-year DFS for patients with RD was 79.7% (95% CI 77.4-80.9). This was higher for trials completing accrual after 2010 [83% (95% CI 79.3-86.3)] and for those receiving dual HER2 targeted therapy [83.4% (95% CI 79.2-87.7]. Better outcomes for ER positivity, later accrual and dual Her-2 targeted therapy were confirmed in meta-regression. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement.
Conclusions: The 3-year DFS for patients with RD has improved over time possibly due to dual HER2 targeted therapy. This will reduce the absolute benefit of adjuvant T-DM1 in this group of patients.
Keywords: Disease-free survival; Dual HER2-targeted therapy; Meta-analysis; Neoadjuvant therapy; Randomized controlled trial.
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