Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial.

This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer. Each patient received four cycles of 260 mg/m2 nab-paclitaxel with 6 mg/kg trastuzumab (8 mg/kg as the loading dose) every 3 weeks (q3w) followed by four cycles of FEC (500/100/500 mg/m2) q3w. The primary endpoint was pathological complete response (pCR) rate. Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%. Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

Tokunaga S ，Takashima T ，Kashiwagi S ，Noda S ，Kawajiri H ，Tokumoto M ，Nishimura S ，Nishimori T ，Ikeda K ，Ogawa Y ，Mizuyama Y ，Sunami T ，Tezuka K ，Yamagata S ，Ishikawa T ，Kudoh S ，Takada M ，Hirakawa K ，Ohira M ... -  《-》

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. Neoadjuvant therapy using this combination appears to be effective and safe.

Tanaka S ，Iwamoto M ，Kimura K ，Matsunami N ，Morishima H ，Yoshidome K ，Nomura T ，Morimoto T ，Yamamoto D ，Tsubota Y ，Kobayashi T ，Uchiyama K ... -  《-》

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial.

Futamura M ，Nagao Y ，Ishihara K ，Takeuchi M ，Nakada T ，Kawaguchi Y ，Asano M ，Kumazawa I ，Shiroko T ，Morimitsu K ，Mori R ，Nawa M ，Shimokawa T ，Yoshida K ... -  《-》

Clinical outcomes of neoadjuvant chemotherapy for patients with breast cancer: Tri-weekly nanoparticle albumin-bound paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide: a retrospective observational study.

Shizuku M ，Shibata M ，Shimizu Y ，Takeuchi D ，Mizuno Y ... -  《Nagoya Journal of Medical Science》

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2(-) Early-stage Breast Cancer.

Weekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) demonstrated greater efficacy with less toxicity than docetaxel in metastatic breast cancer. We conducted a randomized phase II to compare these regimens as neoadjuvant chemotherapy for HER2- early-stage breast cancer. Stage I-III human epidermal growth factor receptor-negative (HER2-) breast cancer patients were included in the present trial and received either docetaxel every 3 weeks or nab-paclitaxel on days 1, 8, and 15 every 28 days for 4 cycles, followed by FEC (5-fluorouracil, epirubicin, cyclophosphamide) every 3 weeks for 4 cycles. The primary endpoint was the pathologic complete response (pCR) rate, defined as ypT0 and ypN0. The secondary endpoints were pCR (ypT0/ypTis and ypN0), the clinical response rate (using the Response Evaluation Criteria In Solid Tumors criteria), histologic effect of treatment (using the Japanese Breast Cancer Society classification), breast conservation rate, and adverse events. A total of 152 eligible patients were enrolled at 6 centers. The baseline characteristics were well balanced. In comparing the 2 regimens (docetaxel/nab-paclitaxel), the pCR rate was 12% and 17% (P = .323). In the Ki67 > 20% group, the pCR rate was greater (24%) for the nab-paclitaxel arm than for the docetaxel arm (16%; P = .432). The most common grade 3/4 adverse event was neutropenia, observed in 40% and 36% of cases in the nab-paclitaxel and docetaxel arms, respectively. The nonhematologic adverse events of any grade were myalgia (34% and 32%), arthralgia (42% and 35%), and peripheral sensory neuropathy (55% and 65%) for the 2 treatment arms. No grade 3/4 peripheral sensory neuropathy was observed in the nab-paclitaxel arm. Weekly nab-paclitaxel administered at a dose of 100 mg/m2 showed equivalent efficacy and was well tolerated compared with docetaxel as neoadjuvant therapy. Nab-paclitaxel might be more effective in patients with highly proliferative cancer.

Kuwayama T ，Nakamura S ，Hayashi N ，Takano T ，Tsugawa K ，Sato T ，Kitani A ，Okuyama H ，Yamauchi H ... -  《-》