TY - JOUR
T1 - Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer
AU - Tsurutani, Junji
AU - Hara, Fumikata
AU - Kitada, Masahiro
AU - Takahashi, Masato
AU - Kikawa, Yuichiro
AU - Kato, Hiroaki
AU - Sakata, Eiko
AU - Naito, Yoichi
AU - Hasegawa, Yoshie
AU - Saito, Tsuyoshi
AU - Iwasa, Tsutomu
AU - Taira, Naruto
AU - Takashima, Tsutomu
AU - Kashiwabara, Kosuke
AU - Aihara, Tomohiko
AU - Mukai, Hirofumi
N1 - Funding Information:
This work was supported by the Comprehensive Support Project for Oncology Research in Breast Cancer. The research fund was provided to the Comprehensive Support Project for Oncology Research in Breast Cancer by Taiho Pharmaceutical under the study contract. Taiho Pharmaceutical took no part in this study other than providing information relevant to proper use of the study drug.
Funding Information:
This work was supported by the Comprehensive Support Project for Oncology Research in Breast Cancer. The research fund was provided to the Comprehensive Support Project for Oncology Research in Breast Cancer by Taiho Pharmaceutical under the study contract. Taiho Pharmaceutical took no part in this study other than providing information relevant to proper use of the study drug.Junji Tsurutani received preclinical research funds from Daiichi Sankyo during this study; and outside the submitted work, received honorarium from Novartis, Taiho, Eisai, Chugai, and Kyowa Kirin; personal fees for participating in advisory boards for Eisai and Asahi Kasei; and support for travel expenses from Daiichi Sankyo. Authors Fumikata Hara, Masahiro Kitada, Masato Takahashi, Yuichiro Kikawa, Hiroaki Kato, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Naruto Taira, Tsutomu Takashima, Kosuke Kashiwabara, Tomohiko Aihara and Hirofumi Mukai have no conflict of interest.We thank all the patients who participated in ABROAD and their families and the investigators and research coordinators at the 41 institutions and the CSPOR-BC. The research fund was provided to CSPOR-BC by Taiho Pharmaceutical Co., Ltd under the study contract. All decisions concerning the planning, implementation and publication of this study were made by the executive committee of this study.
Publisher Copyright:
© 2020
PY - 2021/2
Y1 - 2021/2
N2 - Background: Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods: We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results: One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions: Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.
AB - Background: Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods: We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results: One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions: Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.
KW - Chemotherapy-induced peripheral neuropathy
KW - Metastatic breast cancer
KW - Nab-paclitaxel
KW - Nanoparticle albumin–bound paclitaxel
KW - Solvent-base paclitaxel
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U2 - 10.1016/j.breast.2020.12.002
DO - 10.1016/j.breast.2020.12.002
M3 - Article
C2 - 33341707
AN - SCOPUS:85097888471
SN - 0960-9776
VL - 55
SP - 63
EP - 68
JO - Breast
JF - Breast
ER -
