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Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy

BACKGROUND: Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. METHODS: EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes...

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Autores principales: Rugo, Hope S, Ettl, Johannes, Hurvitz, Sara A, Gonçalves, Anthony, Lee, Kyung-Hun, Fehrenbacher, Louis, Mina, Lida A, Diab, Sami, Woodward, Natasha E, Yerushalmi, Rinat, Goodwin, Annabel, Blum, Joanne L, Martin, Miguel, Quek, Ruben G W, Tudor, Iulia Cristina, Bhattacharyya, Helen, Gauthier, Eric, Litton, Jennifer K, Eiermann, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050154/
https://www.ncbi.nlm.nih.gov/pubmed/32337496
http://dx.doi.org/10.1093/jncics/pkz085
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author Rugo, Hope S
Ettl, Johannes
Hurvitz, Sara A
Gonçalves, Anthony
Lee, Kyung-Hun
Fehrenbacher, Louis
Mina, Lida A
Diab, Sami
Woodward, Natasha E
Yerushalmi, Rinat
Goodwin, Annabel
Blum, Joanne L
Martin, Miguel
Quek, Ruben G W
Tudor, Iulia Cristina
Bhattacharyya, Helen
Gauthier, Eric
Litton, Jennifer K
Eiermann, Wolfgang
author_facet Rugo, Hope S
Ettl, Johannes
Hurvitz, Sara A
Gonçalves, Anthony
Lee, Kyung-Hun
Fehrenbacher, Louis
Mina, Lida A
Diab, Sami
Woodward, Natasha E
Yerushalmi, Rinat
Goodwin, Annabel
Blum, Joanne L
Martin, Miguel
Quek, Ruben G W
Tudor, Iulia Cristina
Bhattacharyya, Helen
Gauthier, Eric
Litton, Jennifer K
Eiermann, Wolfgang
author_sort Rugo, Hope S
collection PubMed
description BACKGROUND: Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. METHODS: EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician’s choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline BRCA1/2 (gBRCA1/2) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety. PROs were evaluated in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) or triple-negative breast cancer (TNBC) subgroups. RESULTS: Of 431 patients, 287 were randomly assigned to talazoparib and 144 to PCT. Prespecified subgroup analyses showed prolonged progression-free survival with talazoparib (HR+/HER2−: hazard ratio = 0.47, 95% confidence interval = 0.32 to 0.71; TNBC: hazard ratio = 0.60, 95% confidence interval = 0.41 to 0.87) and greater objective response rate (odds ratio = 1.97 to 11.89), clinical benefit rate (odds ratio = 2.05 to 7.77), and duration of response with talazoparib in all subgroups. PROs in HR+/HER2− and TNBC subgroups showed consistent overall improvement and delay in time to definitive clinically meaningful deterioration with talazoparib vs PCT. Across subgroups, common adverse events included anemia, fatigue, and nausea with talazoparib and neutropenia, fatigue, and nausea with PCT. Seven patients (2.4%) receiving talazoparib had grade II alopecia and 22.7% had grade I alopecia. CONCLUSIONS: Across all patient subgroups with gBRCA-mutated advanced breast cancer, talazoparib demonstrated clinically significant superiority in outcomes compared with PCT.
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spelling pubmed-70501542020-04-24 Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy Rugo, Hope S Ettl, Johannes Hurvitz, Sara A Gonçalves, Anthony Lee, Kyung-Hun Fehrenbacher, Louis Mina, Lida A Diab, Sami Woodward, Natasha E Yerushalmi, Rinat Goodwin, Annabel Blum, Joanne L Martin, Miguel Quek, Ruben G W Tudor, Iulia Cristina Bhattacharyya, Helen Gauthier, Eric Litton, Jennifer K Eiermann, Wolfgang JNCI Cancer Spectr Article BACKGROUND: Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. METHODS: EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician’s choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline BRCA1/2 (gBRCA1/2) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety. PROs were evaluated in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) or triple-negative breast cancer (TNBC) subgroups. RESULTS: Of 431 patients, 287 were randomly assigned to talazoparib and 144 to PCT. Prespecified subgroup analyses showed prolonged progression-free survival with talazoparib (HR+/HER2−: hazard ratio = 0.47, 95% confidence interval = 0.32 to 0.71; TNBC: hazard ratio = 0.60, 95% confidence interval = 0.41 to 0.87) and greater objective response rate (odds ratio = 1.97 to 11.89), clinical benefit rate (odds ratio = 2.05 to 7.77), and duration of response with talazoparib in all subgroups. PROs in HR+/HER2− and TNBC subgroups showed consistent overall improvement and delay in time to definitive clinically meaningful deterioration with talazoparib vs PCT. Across subgroups, common adverse events included anemia, fatigue, and nausea with talazoparib and neutropenia, fatigue, and nausea with PCT. Seven patients (2.4%) receiving talazoparib had grade II alopecia and 22.7% had grade I alopecia. CONCLUSIONS: Across all patient subgroups with gBRCA-mutated advanced breast cancer, talazoparib demonstrated clinically significant superiority in outcomes compared with PCT. Oxford University Press 2019-10-21 /pmc/articles/PMC7050154/ /pubmed/32337496 http://dx.doi.org/10.1093/jncics/pkz085 Text en © The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contactjournals.permissions@oup.com
spellingShingle Article
Rugo, Hope S
Ettl, Johannes
Hurvitz, Sara A
Gonçalves, Anthony
Lee, Kyung-Hun
Fehrenbacher, Louis
Mina, Lida A
Diab, Sami
Woodward, Natasha E
Yerushalmi, Rinat
Goodwin, Annabel
Blum, Joanne L
Martin, Miguel
Quek, Ruben G W
Tudor, Iulia Cristina
Bhattacharyya, Helen
Gauthier, Eric
Litton, Jennifer K
Eiermann, Wolfgang
Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title_full Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title_fullStr Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title_full_unstemmed Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title_short Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician’s Choice Standard-of-Care Chemotherapy
title_sort outcomes in clinically relevant patient subgroups from the embraca study: talazoparib vs physician’s choice standard-of-care chemotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050154/
https://www.ncbi.nlm.nih.gov/pubmed/32337496
http://dx.doi.org/10.1093/jncics/pkz085
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