Abstract P2-01-07: Combination of pyrotinib with trastuzumab, taxanes and platinum as neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer: a multicenter phase II trial
Authors: Zhou Hao , Wang Lei , Wang Lei , Guo Zhaoji 
Published: March 2023

Abstract
Background: Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine have shown clinically and statistically meaningful progression-free survival and overall survival benefits with acceptable tolerability in patients with HER2-positive metastatic breast cancer in phase 3 trials. In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab, taxanes and platinum in women with HER2-positive early or locally advanced breast cancer. Methods: In this multicenter, single-arm, phase II trial (ChiCTR2000039286), treatment-naive patients with early or locally advanced (T2-3, N0-3, M0) breast cancer received pyrotinib 400 mg once daily, plus trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose), docetaxel (75 mg/m2) or nab-paclitaxel (125 mg/m2), and carboplatin (AUC=5-7) on day 1 of each 21-day cycle for 6 cycles before surgery. All patients also received 1-year adjuvant pyrotinib combined with trastuzumab after surgery. The primary endpoint of the study was total pathological complete response (tpCR, ypT0/is ypN0) rate. The secondary endpoints were breast pathological complete response (bpCR) rate, objective response rate, adverse events (AEs) and invasive disease-free survival. Results: Between October 2020 and March 2022, a total of 35 patients were enrolled from 7 sites. By the data cut-off date on June 29, 2022, two patients withdrew from the study, and one received other anti-tumor therapies. Thirty-two patients received neoadjuvant therapy and surgery (modified intention-to-treat [mITT] population), and 30 of whom completed the 6-cycle neoadjuvant therapy (per-protocol [PP] population). The local pathologist-assessed tpCR rate was 59.4% (19/32) and 60.0% (18/30) in the mITT and PP populations, and bpCR rate was 65.6% (21/32) and 66.7% (20/30) in the mITT and PP populations, respectively. The tpCR rate was 68.8% (11/16) among patients with hormone receptor-negative disease and 50.0% (8/16) among those with hormone receptor-positive disease in the mITT population. Of 30 patients with preoperative imaging assessments, 26 (86.7%) achieved an objective response. Treatment-related AEs (TRAEs) were reported in 34 (97.1%) of 35 patients, with the most common being diarrhea (82.9%) and platelet decreased (48.6%). The most common grade ≥3 TRAEs were diarrhea (25.7%), platelet decreased (8.6%), neutropenia (8.6%), vomiting (5.7%), and alanine aminotransferase increased (5.7%). No grade 4 or 5 diarrhea events occurred. Conclusions: This study showed similar efficacy with previous reports, neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with HER2-positive early or locally advanced breast cancer.
Citation Format: Hao Zhou, Lei Wang, Lei Wang, Zhaoji Guo. Combination of pyrotinib with trastuzumab, taxanes and platinum as neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer: a multicenter phase II trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-07.