Cargando…

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study

PURPOSE: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIEN...

Descripción completa

Detalles Bibliográficos
Autores principales: Im, Seock-Ah, Mukai, Hirofumi, Park, In Hae, Masuda, Norikazu, Shimizu, Chikako, Kim, Sung-Bae, Im, Young-Hyuck, Ohtani, Shoichiro, Huang Bartlett, Cynthia, Lu, Dongrui R., Iyer, Shrividya, Mori, Yuko, Mori, Ave, Gauthier, Eric, Finn, Richard S., Toi, Masakazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550032/
https://www.ncbi.nlm.nih.gov/pubmed/31125276
http://dx.doi.org/10.1200/JGO.18.00173
_version_ 1783424115042942976
author Im, Seock-Ah
Mukai, Hirofumi
Park, In Hae
Masuda, Norikazu
Shimizu, Chikako
Kim, Sung-Bae
Im, Young-Hyuck
Ohtani, Shoichiro
Huang Bartlett, Cynthia
Lu, Dongrui R.
Iyer, Shrividya
Mori, Yuko
Mori, Ave
Gauthier, Eric
Finn, Richard S.
Toi, Masakazu
author_facet Im, Seock-Ah
Mukai, Hirofumi
Park, In Hae
Masuda, Norikazu
Shimizu, Chikako
Kim, Sung-Bae
Im, Young-Hyuck
Ohtani, Shoichiro
Huang Bartlett, Cynthia
Lu, Dongrui R.
Iyer, Shrividya
Mori, Yuko
Mori, Ave
Gauthier, Eric
Finn, Richard S.
Toi, Masakazu
author_sort Im, Seock-Ah
collection PubMed
description PURPOSE: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIENTS AND METHODS: Of 666 enrolled postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety. RESULTS: Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.49; 95% CI, 0.27 to 0.87; P = .007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer–specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v –0.069; P = .0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL). CONCLUSION: Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL.
format Online
Article
Text
id pubmed-6550032
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher American Society of Clinical Oncology
record_format MEDLINE/PubMed
spelling pubmed-65500322019-06-07 Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study Im, Seock-Ah Mukai, Hirofumi Park, In Hae Masuda, Norikazu Shimizu, Chikako Kim, Sung-Bae Im, Young-Hyuck Ohtani, Shoichiro Huang Bartlett, Cynthia Lu, Dongrui R. Iyer, Shrividya Mori, Yuko Mori, Ave Gauthier, Eric Finn, Richard S. Toi, Masakazu J Glob Oncol ORIGINAL REPORT PURPOSE: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIENTS AND METHODS: Of 666 enrolled postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety. RESULTS: Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.49; 95% CI, 0.27 to 0.87; P = .007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer–specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v –0.069; P = .0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL). CONCLUSION: Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL. American Society of Clinical Oncology 2019-05-24 /pmc/articles/PMC6550032/ /pubmed/31125276 http://dx.doi.org/10.1200/JGO.18.00173 Text en © 2019 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle ORIGINAL REPORT
Im, Seock-Ah
Mukai, Hirofumi
Park, In Hae
Masuda, Norikazu
Shimizu, Chikako
Kim, Sung-Bae
Im, Young-Hyuck
Ohtani, Shoichiro
Huang Bartlett, Cynthia
Lu, Dongrui R.
Iyer, Shrividya
Mori, Yuko
Mori, Ave
Gauthier, Eric
Finn, Richard S.
Toi, Masakazu
Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title_full Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title_fullStr Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title_full_unstemmed Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title_short Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study
title_sort palbociclib plus letrozole as first-line therapy in postmenopausal asian women with metastatic breast cancer: results from the phase iii, randomized paloma-2 study
topic ORIGINAL REPORT
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6550032/
https://www.ncbi.nlm.nih.gov/pubmed/31125276
http://dx.doi.org/10.1200/JGO.18.00173
work_keys_str_mv AT imseockah palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT mukaihirofumi palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT parkinhae palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT masudanorikazu palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT shimizuchikako palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT kimsungbae palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT imyounghyuck palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT ohtanishoichiro palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT huangbartlettcynthia palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT ludongruir palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT iyershrividya palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT moriyuko palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT moriave palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT gauthiereric palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT finnrichards palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study
AT toimasakazu palbociclibplusletrozoleasfirstlinetherapyinpostmenopausalasianwomenwithmetastaticbreastcancerresultsfromthephaseiiirandomizedpaloma2study