Pathologic complete response rate and predictors of response to neoadjuvant THP in HER2-positive breast cancer

The multinational EA1181 trial evaluated neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa HER2-positive breast cancer. The primary endpoint – 3-year recurrence-free survival among patients achieving a pathologic complete response (pCR) – will be reported when data mature. Secondary endpoints of pCR rates and associated factors have now been published. Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel for 12 weeks or docetaxel every 3 weeks for four cycles, followed by surgery. A total of 2175 patients were enrolled (781 HER2+/ER-; 1394 HER+/ER+). Of 2141 patients who initiated THP, the overall pCR rate was 43.8%; 63.7% in HER2+/ER- and 32.4% in HER2+/ER+. Higher pCR rates were observed in tumors that were ER- or low ER expressing, PR- or low PR expressing, HER2 IHC 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER- tumors; otherwise tumor and nodal stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rate after adjustment for clinicopathologic variables. The authors conclude that these findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.