Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study)

Manabu Futamura,Uhi Toh,Kazuhiko Yamagami,Morihito Okada,Takashi Kuwayama,Takeshi Nagashima,Masafumi Inokuchi,Hiroko Bando,Yutaka Mizuno,Yutaka Yamamoto,Mari Oba,Takanori Kin,Hiroyuki Yasojima,Yasuyuki Kojima,Takahiro Nakayama,Shinji Ohno,Toshiaki Saeki,Norikazu Masuda,Akira Hirano

doi:10.1007/s12282-021-01238-9

Abstract

BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies.MethodsWe conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype.ResultsWe analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered.ConclusionsNab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774

Highlights

Taxane is a current gold standard chemotherapeutic agent for breast cancer (BC), adverse events (AEs) such as peripheral neuropathy and hypersensitivity are often problematic for patients
As taxol plays an important role in BC therapy, Nanoparticle albumin-bound paclitaxel (nab-PTX) was first utilized for metastatic BC, resulting in longer progression-free survival (PFS) than that achieved with either paclitaxel or docetaxel [4, 5]
We found 35 studies in the UMIN-CTR, which were reviewed using the PRISMA individual patient data (IPD) flow diagram shown in Fig. 1a [19]

Summary

Introduction

Taxane is a current gold standard chemotherapeutic agent for breast cancer (BC), adverse events (AEs) such as peripheral neuropathy and hypersensitivity are often problematic for patients. Breast Cancer (2021) 28:1023–1037 myalgia, and peripheral neuropathy, but they are transient and controllable [5] These reports suggest wide applications of nab-PTX for BC therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. Methods We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTXcontaining regimens as neoadjuvant chemotherapy for operable breast cancer. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered.

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