A phase 2 study of de-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low risk pure HER2 breast cancer

Background: Neoadjuvant anti-HER2 target agents combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. Patients and Methods: We treated patients with tumors measuring ≤3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. The accrual of 30 patients was planned. This study was registered with ClinicalTrials.gov, number NCT02598310 and University hospital Medical Information Network-Clinical Trials Registry, number UMIN000019616. Results: This study was terminated without the expected number owing to slow accrual. In total, 18 patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. Observed grade 3 adverse events included neutropenia (6%), liver enzyme elevation (11%), and allergic reaction to infusion of trastuzumab (6%). Notably, sensory peripheral neuropathy was observed in a substantial number of patients (88%), but there were no severe events. Discussion: The primary outcome observed in this study is not inferior to that reported in previous studies which were administered the standard regimens with trastuzumab combined with anthracycline and taxane. Therapeutic strategies that achieve pCR using efficient and effective neoadjuvant therapy with fewer adverse effects and lower cost are advantageous. On the other hand, originally, as many patients with small tumors who met eligible criteria of this study does not need mastectomy, they are less likely to benefit from breast conserving surgery due to tumor shrinkage effect by neoadjuvant therapy. It is conceivable that there were a certain number of patients who selected primary surgery rather than neoadjuvant therapy of this study. In conclusion, this less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk. Citation Format: Satoru Tanaka, Hirotaka Morishima, Naofumi Oda, Nobuki Matsunami, Tsutomu Takashima, Satoru Noda, Shinichiro Kashiwagi, Yukie Tauchi, Yuka Asano, Kosei Kimura, Hiruya Fujioka, Risa Terasawa, Kanako Kawaguchi, Ayana Ikari, Takashi Morimoto, Shintaro Michishita, Toshihiro Kobayashi, Junna Sakane, Toshikatsu Nitta, Nayuko Sato, Norihiro Hokimoto, Yukihiro Nishida, Mitsuhiko Iwamoto. A phase 2 study of de-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low risk pure HER2 breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-32.