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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Clinical Oncology
2019
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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 |
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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 |
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