Abstract P2-16-13: Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01)
Authors: Futamura Manabu , Oba Mari , Masuda Norikazu , Bando Hiroko , Yamamoto Yutaka , Kin Takanori , Saeki Toshiaki , Nagashima Takeshi , Kuwayama Takashi , Toh Uhi , Hirano Akira , Inokuchi Masafumi , Yamagami Kazuhiko , Mizuno Yutaka , Kojima Yasuyuki , Nakayama Takahiro , Yasojima Hiroyuki , Okada Morihito , Ohno Shinji 
Published: March 2020

[Background] Nanoparticle albumin-bound paclitaxel (Nab-PTX) is a novel taxane formulation that was developed to avoid Cremophor/ethanol associated toxicities such as peripheral neuropathy and hypersensitive reactions. Since Taxol plays an important role in breast cancer therapy, Nab-PTX is considered safe and effective for metastatic breast cancer (MBC). According to these reports, a regimen including Nab-PTX in a neoadjuvant setting may induce preferable results. Several recent reports using a combination of Nab-PTX and anthracycline in neoadjuvant chemotherapy (NAC) have been published. In Japan, at least 34 small phase II studies using a Nab-PTX regimen have been registered with the University hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR). We believe that integration of these data is important to evaluate the power of Nab-PTX, so we conducted a meta-analysis based on individual patient data (IPD). [Materials and Methods] This study is a collaborative meta-analysis of single arm trials using IPD to summarize the published and unpublished evidence of Nab-PTX-containing regimen efficacy. The main objective was to assess the rate of pathological complete response (pCR). Definitions of pCR were (1) ypT0 ypN0, (2) ypT0/is ypN0, and (3) ypT0/is ypNX. The secondary objectives were adverse events (AEs) (≥G3) and dose of administered Nab-PTX (mg/m2). First, we found 34 phase II studies registered from Feb 2011 to Jun 2016 using an electron search of UMIN-CTR. Second, we contacted each principal investigator (PI) to ask if they would participate in this study by providing individual data. Inclusion criteria were as follows: (1) Clinical trial(s) started after July 2010, (2) Principal investigator(s) in each trial agreed with study participation, (3) Nab-PTX-containing regimen was used for neoadjuvant chemotherapy in naive operable breast cancer patients, (4) Registered in UMIN with ethical review, (5) Clinical trials with more than 10 patients, (6) Completed clinical trials only were included (unpublished data are available), and (7) Each researcher was authorized by the research ethics committee to submit the data. pCR rates in all cases/each subtype were calculated with a 95% confidence interval (CI). The proportion of AEs and total Nab-PTX dose were also calculated. [Results] Among 34 studies, 16 studies (4 published, 12 unpublished) included 758 patients. Among these 16 studies, 5 (2 metastatic, 3 no treatment) were excluded for all analyses (n=753). After excluding 8 (3 declined surgery, 1 hospital transfer, 4 unknown), a total of 745 (including 2 PD, 1 death) were analyzed for the primary analysis. All HER2-positive cases were treated by combining Nab-PTX and trastuzumab. Crude overall percentages of pCR (ypT0ypN0, ypT0/isypN0, and ypT0/isypNX) were 18.1%, 26.0%, and 28.6%, respectively. In detail, 6.7%, 10.2%, and 13.4% for Luminal type (n=343), 26.3%, 31.5%, and 32.3% for triple negative (TNBC, n=232), 40.5%, 63.5%, and 68.9% for HER2-rich (n=74), 21.9%, 40.6%, and 42.7% for Luminal/HER2 type (n=96), respectively. AEs (≥G3) were observed as follows: 41.5% neutropenia, 32.3% leukopenia, 10.6% febrile neutropenia, 10.6% peripheral sensory neuropathy, 2.5% peripheral motor neuropathy, 6.4% myalgia, 5.5% arthralgia, 6.1% hepatobiliary disorders, 4.5% vomiting, 0.7%, cardiac disorders, and 0.9% infusion reaction. Only one patient died during FEC followed by Nab-PTX. [Conclusion] NAC regimen containing Nab-PTX was safe, and the efficacy was equal to or greater than regimens containing other taxanes. The combination Nab-PTX and trastuzumab is particularly useful and powerful against the HER2-positive subtype. However, the Nab-PTX-containing regimen is not as powerful against TNBC in a neoadjuvant setting.

Citation Format: Manabu Futamura, Mari Oba, Norikazu Masuda, Hiroko Bando, Yutaka Yamamoto, Takanori Kin, Toshiaki Saeki, Takeshi Nagashima, Takashi Kuwayama, Uhi Toh, Akira Hirano, Masafumi Inokuchi, Kazuhiko Yamagami, Yutaka Mizuno, Yasuyuki Kojima, Takahiro Nakayama, Hiroyuki Yasojima, Morihito Okada, Shinji Ohno. Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01) [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 P2-16-13.