Efficacy and safety of neoadjuvant pertuzumab, trastuzumab and chemotherapy in non-metastatic HER2-positive breast cancer in the Asian population: a multicentre analysis

Abstract

Background: Pertuzumab combined with trastuzumab and chemotherapy is now the standard neoadjuvant treatment for non-metastatic HER2-positive early breast cancer (HER2+ BC). However, information on the efficacy of this combination in Asian population is sparse. This retrospective study aims to assess the clinical outcome of adding pertuzumab to trastuzumab and chemotherapy (PH/CTX) for stage II to III HER2+ BC in an Asian cohort. Methods: A multi-centre, retrospective study on pre-treatment clinical stage II-III, HER2+ BC patients treated with neoadjuvant PH/CTX from January 2013 to June 2019 in six oncology centres in Hong Kong was performed. Demographic data, size, grade, tumor type, hormonal receptor (HR) status, concomitant chemotherapy used, cycles of systemic treatment and pathological complete response (pCR) rates were analyzed. pCR was defined as the absence of invasive or noninvasive cancer in breast and lymph nodes, i.e., ypT0ypN0. Results: A total of 211 patients received neoadjuvant PH/CTX, median age: 52 year old (range: 26–83). 90 patients (42.7%) were in clinical stage II and 121 (57.3%) patients were in clinical stage III. 134 (63.5%) patients had HR+ tumors. The concomitant chemotherapy regimens included doxycycline-carboplatin (DC) (165, 78.2%), paclitaxel-carboplatin (TC) (33, 15.6%), and adriamycin-cyclophosphamide then doxycycline-carboplatin (AC-DC) (13, 6.2%). The median number of cycles of neoadjuvant PH given was 6 (range 4–8). 197 patients had radical surgery after neoadjuvant PH/CTX (7 patients: refused operation; 7 patients had persistent inoperable disease or progression). 115 patients achieved pCR after neoadjuvant PH/CTX (overall pCR rate: 58.4%). pCR was higher in HR- tumors (HR+ vs. HR-: 52.3% vs. 70.8%, p = 0.014) and smaller tumors (OR: 0.99, 95% CI 0.97–1.0, p = 0.02). For the chemotherapy partner, adding anthracycline on top of taxane-based chemotherapy did not improve the pCR rate (pCR rate of DC: 57.1%; TC: 67.9%; AC-DC: 50%, p = 0.73). Among 78 patients with clinically inoperable locally advanced disease, 69 patients (88.5%) had good response after neoadjuvant PH/CTX and underwent radical operation with clear resection margin; 41 patients (52.6%) achieved pCR. HR status, size of tumor, N stage, Ki-67 level or chemotherapy partner were not associated with pCR rate in locally advanced disease. Conclusion: Neoadjuvant PH/CTX was associated with a pCR rate of 58.4% in our Asian cohort. Results in locally advanced disease were promising. The conversion rate of initially inoperable disease to operable disease was high and the pCR rate was over 50%.