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Background: Despite that dual anti-HER2 therapy (Trastuzumab and Pertuzumab, TP) is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that its pCR rate rarely exceeds 63%. Additionally, it is associated with higher risk of cardiac adverse events. TQB2440, a biosimilar of pertuzumab, with strong affinity and specificity, can effectively bind with HER2 epitope. In the PDX mouse model, TQB2440 showed promising biological activity and minimal cardiotoxicity. In this study, we designed a single-arm trial of dual anti-HER2 therapy (TQB2440 and trastuzumab, TT) plus docetaxel in neoadjuvant therapy of HER2 positive breast cancer. We aimed to examine the efficacy and safety of TQB2440 and study whether new dual anti-HER2 therapy (TT) can boost pCR rate in the neoadjuvant treatment. The cardiotoxicity and other adverse reactions were closely monitored. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HR negative HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy were enrolled. The patients were treated with docetaxel 75 mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, TQB2440 840 mg loading, then 420 mg, iv, q3w for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity. Results: From April 2021 to February 2022, a total of 28 patients were recruited. Among the 28 patients with a median age of 52 (28-74), 12 patients had positive lymph node status. Overall, the pCR rate was 67.9% (19/28). The pCR rate was higher than that in the NeoSphere trial (pCR 63.2%) and the PEONY study (pCR 52.5%). The lymph-positive tumor achieved a higher pCR rate than lymph-negative tumor (70.8% vs 52.3%, p = .019). Multivariate regression analysis showed that for participants aged 50 or above, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were leukopenia (46.4%), neutropenia (35.7%), asthenia (3.6%), and peripheral sensory neuropathy (2.3%). Left ventricular insufficiency was detected in 1 patient, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusion: TQB2440 and trastuzumab plus docetaxel is a feasible and effective neoadjuvant therapy for early-stage HR negative HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for dual anti-HER2 therapy using TQB2440 in neoadjuvant or adjuvant therapy of HER2 positive breast cancer. Citation Format: Jiang Wu, Jing Yu, Yuqing Yang, Xinxin Wen, Jixin Yang, Hongliang Wei, Xiaolong Xu, Yike Li, Liu Yang, Dongdong Xu, Lei Wang, Yijia Wang, Wen Ma, Nanlin Li. Efficacy and safety of neoadjuvant pertuzumab biosimilar TQB2440, trastuzumab and docetaxel in HR negative, HER2 positive breast cancer: a single-arm 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 P3-07-25. |
