Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783410550267445248 |
---|---|
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 |
format | Online Article Text |
id | pubmed-6461876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fujiwarayasuhiro amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT mukaihirofumi amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT saekitoshiaki amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT rojungsil amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT linyungchang amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT nagaishigenorie amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT leekeunseok amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT watanabejunichiro amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT ohtanishoichiro amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT kimsungbae amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT kuroikatsumasa amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT tsugawakoichiro amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT tokudayutaka amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT iwatahiroji amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT parkyeonhee amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT yangyoungsen amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT nambuyoshihiro amultinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT fujiwarayasuhiro multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT mukaihirofumi multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT saekitoshiaki multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT rojungsil multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT linyungchang multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT nagaishigenorie multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT leekeunseok multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT watanabejunichiro multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT ohtanishoichiro multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT kimsungbae multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT kuroikatsumasa multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT tsugawakoichiro multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT tokudayutaka multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT iwatahiroji multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT parkyeonhee multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT yangyoungsen multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients AT nambuyoshihiro multinationalrandomisedopenlabelparallelphaseiiinoninferioritystudycomparingnk105andpaclitaxelinmetastaticorrecurrentbreastcancerpatients |