Pathologic complete response (pCR) rate and factors associated with pCR after taxane, trastuzumab, and pertuzumab in HER2-positive breast cancer: secondary analyses of EA1181
TL;DR
Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER− and one-third with HER2+/ER+ breast cancer, and these findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.
Abstract
Background: EA1181 (NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa HER2-positive breast cancer. This report focuses on the secondary endpoints of pCR rates and associated factors. The primary endpoint—3-year recurrence-free survival (RFS) among patients achieving a pathologic complete response (pCR; ypT0/Tis, ypN0)—will be reported when data mature. Methods: Patients received four cycles of trastuzumab and pertuzumab (HP) with either weekly paclitaxel (12 weeks) or docetaxel (every 3 weeks for 4 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 HER2+/ER−; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER− and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER-expressing, PR-negative or low-expressing, HER2 IHC 3+, and in patients treated with weekly paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER− tumors; otherwise, tumor (T) and nodal (N) stage did not significantly impact 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 HER2+/ER− and one-third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, weekly 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.