Pathologic Complete Response (pCR) Rate and Predictors ofResponse to Taxane, Trastuzumab, and Pertuzumab inHER2‑Positive Breast Cancer: Secondary Analyses ofEA1181/CompassHER2 pCR

ABSTRACT
PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature.
METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors
associated with pCR.
RESULTS A total of 2,175 patients were enrolled (781 HER21/estrogen receptor‑negative [ER–]; 1,394 HER21/ER1). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER21/ER– and 32.4% in HER21/ER1 tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 31, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER21/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables.
CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER21/ ER– and one third with HER21/ER1 breast cancer. Low hormone receptor expression, HER2 IHC 31 status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with
HER2-positive breast cancer.