Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).

person Jixin Yang Xijing Hospital, Xi'an, China info_outline Jixin Yang, Yuqing Yang, Xinxin Wen, Jiang Wu, Jing Yu, Lei Wang, Meiling Huang, Wenyu Hu, Wen Ma, Nanlin Li

Authors person Jixin Yang Xijing Hospital, Xi'an, China info_outline Jixin Yang, Yuqing Yang, Xinxin Wen, Jiang Wu, Jing Yu, Lei Wang, Meiling Huang, Wenyu Hu, Wen Ma, Nanlin Li Organizations Xijing Hospital, Xi'an, China Abstract Disclosures Research Funding Other Foundation Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m 2 , cyclophosphamide 600mg/m 2 , trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m 2 , trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.