Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04)

• Published in: Breast cancer (Tokyo, Japan) Vol. 30; no. 2; pp. 293 - 301
• Main Authors: Futamura, Manabu, Ishihara, Kazuhiro, Nagao, Yasuko, Ogiso, Atsuko, Niwa, Yoshimi, Nakada, Takumi, Kawaguchi, Yoshihiro, Ikawa, Ai, Kumazawa, Iwao, Mori, Ryutaro, Kitazawa, Mai, Hosono, Yoshiki, Kuno, Masashi, Kawajiri, Mana, Nakakami, Akira, Takeuchi, Makoto, Morikawa, Akemi, Tokumaru, Yoshihisa, Katagiri, Yasuo, Asano, Yoshimasa, Mushika, Yoshinori, Shimokawa, Toshio, Matsuhasih, Nobuhisa
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-03-2023; Springer
• Subjects: Adjuvant treatment; Albumin; Albumin-Bound Paclitaxel; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - pathology; Cancer; Cancer Research; Clinical trials; Cyclophosphamide; Cyclophosphamide - adverse effects; Epidermal growth factor; Epirubicin - adverse effects; Female; Humans; Medicine; Medicine & Public Health; Middle Aged; Nanoparticles; Neoadjuvant Therapy; Neutropenia - chemically induced; Oncology; Original; Original Article; Paclitaxel - adverse effects; Pertuzumab; Product development; Receptor, ErbB-2 - metabolism; Surgery; Surgical Oncology; Trastuzumab - adverse effects; Albumin-bound paclitaxel (Nab-PTX); Neoadjuvant chemotherapy; HER2-positive breast cancer; Pertuzumab; Trastuzumab
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-022-01425-2

Background
Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC).
Methods
In this multicenter phase II clinical trial (January 2019–July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples.
Results
In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6–64.1%,
p
 = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1–86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1–61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples.
Conclusion
Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.