Abstract P1-18-01: Risk of recurrence and death in patients with early HER2-positive breast cancer who achieve a pathological complete response (pCR) after different types of HER2-targeted therapy: A retrospective exploratory analysis
Authors: Swain Sandra M , Macharia Harrison , Cortes Javier , Dang Chau , Gianni Luca , Hurvitz Sara , Jackisch Christian , Schneeweiss Andreas , Slamon Dennis , Valagussa Pinuccia , du Toit Yolande , Heinzmann Dominik , Knott Adam , Song Chunyan , Cortazar Patricia 
Published: March 2020

Abstract
Background: The current standard of care for patients achieving a pCR after HER2-targeted therapy plus chemotherapy in the neoadjuvant setting is to continue HER2-targeted therapy in the adjuvant setting. The aim of this exploratory data analysis is to report the risk of recurrence and death after neoadjuvant systemic therapy in Roche-sponsored neoadjuvant trials in patients with HER2-positive early breast cancer who achieved a pCR.
Methods: Data from the HannaH (NCT00950300), NeoSphere (NCT00545688), TRYPHAENA (NCT00976989), BERENICE (NCT02132949), and KRISTINE (NCT02131064) studies were pooled. Neoadjuvant → adjuvant therapeutic regimens analyzed were trastuzumab → trastuzumab (H→H), pertuzumab plus trastuzumab → trastuzumab (PH→H), and pertuzumab plus trastuzumab → pertuzumab plus trastuzumab (PH→PH). pCR was defined as the absence of residual invasive cancer in the resected breast specimen and in the axillary lymph nodes (ypT0/Tis ypN0) after neoadjuvant systemic therapy. Event-free survival (EFS) was defined as the time from the date of randomization to the date of disease recurrence or progression (local, regional, distant, or contralateral) or death due to any cause. EFS rates were estimated using the Kaplan-Meier method. A Cox regression model was used to explore factors associated with EFS.
Results: 1764 patients were included in the analysis. The median duration of follow up was shorter in the PH→PH group compared to the PH→H and H→H groups (Table). Overall, patients with a pCR had an increased EFS probability compared to those with residual disease (unadjusted hazard ratio=0.33; 95% confidence interval [CI]: 0.25– 0.43]), and this was maintained in patients stratified by hormone receptor status and disease stage. The 3-year EFS rates in patients who achieved a pCR were 87% (95% CI: 82%–90%) in the H→H group, 92% (95% CI: 87%–95%) in the PH→H group, and 95% (95% CI: 90%–97%) in the PH→PH group.
Conclusions: Overall, patients who attained a pCR have a better long-term outcome compared to those with residual disease, regardless of ER status or clinical stage. Some patients who achieved a pCR still had a risk of relapse. A limitation of this exploratory data analysis was the smaller number of patients with stage III disease at baseline and shorter follow-up in the PH→PH group compared to the other groups.
Overall(N=1764)H→H (HannaH; NeoSPHERE)(n=703)PH→H (NeoSPHERE; TRYPHAENA)(n=439)PH→PH (BERENICE; KRISTINE)(n=622)Median Duration of Follow-up (months)42.067.961.122.3Disease StageStage II934 (52.9)285 (40.5)204 (46.5)445 (71.5)Stage III806 (45.7)397 (56.5)235 (53.5)174 (28.0)Hormone Receptor StatusPositive783 (44.4)328 (46.7)223 (50.8)232 (37.3)Negative963 (54.6)372 (52.9)215 (49.0)376 (60.5)Unknown18 (1.0)3 (0.4)1 (0.2)14 (2.3)pCR status773 (43.8)236 (33.6)185 (42.1)352 (56.6)Type of recurrence in patients who achieved a pCRDistant recurrence41 (5.3)26 (11.0)10 (5.4)5 (1.4)Local recurrence17 (2.2)12 (5.1)5 (2.7)0Regional recurrence6 (0.8)3 (1.3)2 (1.1)1 (0.3)New contralateral breast cancer2 (0.3)2 (0.8)00
Citation Format: Sandra M Swain, Harrison Macharia, Javier Cortes, Chau Dang, Luca Gianni, Sara Hurvitz, Christian Jackisch, Andreas Schneeweiss, Dennis Slamon, Pinuccia Valagussa, Yolande du Toit, Dominik Heinzmann, Adam Knott, Chunyan Song, Patricia Cortazar. Risk of recurrence and death in patients with early HER2-positive breast cancer who achieve a pathological complete response (pCR) after different types of HER2-targeted therapy: A retrospective exploratory analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-01.