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A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients

BACKGROUND: NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer. METHODS: Patients wer...

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Autores principales: Fujiwara, Yasuhiro, Mukai, Hirofumi, Saeki, Toshiaki, Ro, Jungsil, Lin, Yung-Chang, Nagai, Shigenori E., Lee, Keun Seok, Watanabe, Junichiro, Ohtani, Shoichiro, Kim, Sung Bae, Kuroi, Katsumasa, Tsugawa, Koichiro, Tokuda, Yutaka, Iwata, Hiroji, Park, Yeon Hee, Yang, Youngsen, Nambu, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461876/
https://www.ncbi.nlm.nih.gov/pubmed/30745582
http://dx.doi.org/10.1038/s41416-019-0391-z
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author Fujiwara, Yasuhiro
Mukai, Hirofumi
Saeki, Toshiaki
Ro, Jungsil
Lin, Yung-Chang
Nagai, Shigenori E.
Lee, Keun Seok
Watanabe, Junichiro
Ohtani, Shoichiro
Kim, Sung Bae
Kuroi, Katsumasa
Tsugawa, Koichiro
Tokuda, Yutaka
Iwata, Hiroji
Park, Yeon Hee
Yang, Youngsen
Nambu, Yoshihiro
author_facet Fujiwara, Yasuhiro
Mukai, Hirofumi
Saeki, Toshiaki
Ro, Jungsil
Lin, Yung-Chang
Nagai, Shigenori E.
Lee, Keun Seok
Watanabe, Junichiro
Ohtani, Shoichiro
Kim, Sung Bae
Kuroi, Katsumasa
Tsugawa, Koichiro
Tokuda, Yutaka
Iwata, Hiroji
Park, Yeon Hee
Yang, Youngsen
Nambu, Yoshihiro
author_sort Fujiwara, Yasuhiro
collection PubMed
description BACKGROUND: NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer. METHODS: Patients were randomly assigned in a 1:1 ratio to receive either NK105 (65 mg/m(2)) or PTX (80 mg/m(2)) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS), with a non-inferiority margin of 1.215. RESULTS: A total of 436 patients were randomised and 211 patients in each group were included in the efficacy analysis. The median PFS was 8.4 and 8.5 months for NK105 and PTX, respectively (adjusted hazard ratio: 1.255; 95% confidence interval: 0.989–1.592). The median overall survival and overall response rates were 31.2 vs. 36.2 months and 31.6% vs. 39.0%, respectively. The two groups exhibited similar safety profiles. The incidence of peripheral sensory neuropathy (PSN) was 1.4% vs. 7.5% (≥Grade 3) for NK105 and PTX, respectively. The patient-reported outcomes of PSN were significantly favourable for NK105 (P < 0.0001). CONCLUSIONS: The primary endpoint was not met, but NK105 had a better PSN toxicity profile than PTX. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01644890
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spelling pubmed-64618762019-09-11 A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients Fujiwara, Yasuhiro Mukai, Hirofumi Saeki, Toshiaki Ro, Jungsil Lin, Yung-Chang Nagai, Shigenori E. Lee, Keun Seok Watanabe, Junichiro Ohtani, Shoichiro Kim, Sung Bae Kuroi, Katsumasa Tsugawa, Koichiro Tokuda, Yutaka Iwata, Hiroji Park, Yeon Hee Yang, Youngsen Nambu, Yoshihiro Br J Cancer Article BACKGROUND: NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer. METHODS: Patients were randomly assigned in a 1:1 ratio to receive either NK105 (65 mg/m(2)) or PTX (80 mg/m(2)) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS), with a non-inferiority margin of 1.215. RESULTS: A total of 436 patients were randomised and 211 patients in each group were included in the efficacy analysis. The median PFS was 8.4 and 8.5 months for NK105 and PTX, respectively (adjusted hazard ratio: 1.255; 95% confidence interval: 0.989–1.592). The median overall survival and overall response rates were 31.2 vs. 36.2 months and 31.6% vs. 39.0%, respectively. The two groups exhibited similar safety profiles. The incidence of peripheral sensory neuropathy (PSN) was 1.4% vs. 7.5% (≥Grade 3) for NK105 and PTX, respectively. The patient-reported outcomes of PSN were significantly favourable for NK105 (P < 0.0001). CONCLUSIONS: The primary endpoint was not met, but NK105 had a better PSN toxicity profile than PTX. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01644890 Nature Publishing Group UK 2019-02-12 2019-03-05 /pmc/articles/PMC6461876/ /pubmed/30745582 http://dx.doi.org/10.1038/s41416-019-0391-z Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fujiwara, Yasuhiro
Mukai, Hirofumi
Saeki, Toshiaki
Ro, Jungsil
Lin, Yung-Chang
Nagai, Shigenori E.
Lee, Keun Seok
Watanabe, Junichiro
Ohtani, Shoichiro
Kim, Sung Bae
Kuroi, Katsumasa
Tsugawa, Koichiro
Tokuda, Yutaka
Iwata, Hiroji
Park, Yeon Hee
Yang, Youngsen
Nambu, Yoshihiro
A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title_full A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title_fullStr A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title_full_unstemmed A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title_short A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
title_sort multi-national, randomised, open-label, parallel, phase iii non-inferiority study comparing nk105 and paclitaxel in metastatic or recurrent breast cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461876/
https://www.ncbi.nlm.nih.gov/pubmed/30745582
http://dx.doi.org/10.1038/s41416-019-0391-z
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