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Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population

PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patient...

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Autores principales: De Laurentiis, Michelino, Borstnar, Simona, Campone, Mario, Warner, Ellen, Bofill, Javier Salvador, Jacot, William, Dent, Susan, Martin, Miguel, Ring, Alistair, Cottu, Paul, Lu, Janice, Ciruelos, Eva, Azim, Hamdy A., Chatterjee, Sanjoy, Zhou, Katie, Wu, Jiwen, Menon-Singh, Lakshmi, Zamagni, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505291/
https://www.ncbi.nlm.nih.gov/pubmed/34414532
http://dx.doi.org/10.1007/s10549-021-06334-0
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author De Laurentiis, Michelino
Borstnar, Simona
Campone, Mario
Warner, Ellen
Bofill, Javier Salvador
Jacot, William
Dent, Susan
Martin, Miguel
Ring, Alistair
Cottu, Paul
Lu, Janice
Ciruelos, Eva
Azim, Hamdy A.
Chatterjee, Sanjoy
Zhou, Katie
Wu, Jiwen
Menon-Singh, Lakshmi
Zamagni, Claudio
author_facet De Laurentiis, Michelino
Borstnar, Simona
Campone, Mario
Warner, Ellen
Bofill, Javier Salvador
Jacot, William
Dent, Susan
Martin, Miguel
Ring, Alistair
Cottu, Paul
Lu, Janice
Ciruelos, Eva
Azim, Hamdy A.
Chatterjee, Sanjoy
Zhou, Katie
Wu, Jiwen
Menon-Singh, Lakshmi
Zamagni, Claudio
author_sort De Laurentiis, Michelino
collection PubMed
description PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2– ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-021-06334-0.
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spelling pubmed-85052912021-10-19 Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population De Laurentiis, Michelino Borstnar, Simona Campone, Mario Warner, Ellen Bofill, Javier Salvador Jacot, William Dent, Susan Martin, Miguel Ring, Alistair Cottu, Paul Lu, Janice Ciruelos, Eva Azim, Hamdy A. Chatterjee, Sanjoy Zhou, Katie Wu, Jiwen Menon-Singh, Lakshmi Zamagni, Claudio Breast Cancer Res Treat Clinical Trial PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2– ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-021-06334-0. Springer US 2021-08-19 2021 /pmc/articles/PMC8505291/ /pubmed/34414532 http://dx.doi.org/10.1007/s10549-021-06334-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Trial
De Laurentiis, Michelino
Borstnar, Simona
Campone, Mario
Warner, Ellen
Bofill, Javier Salvador
Jacot, William
Dent, Susan
Martin, Miguel
Ring, Alistair
Cottu, Paul
Lu, Janice
Ciruelos, Eva
Azim, Hamdy A.
Chatterjee, Sanjoy
Zhou, Katie
Wu, Jiwen
Menon-Singh, Lakshmi
Zamagni, Claudio
Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title_full Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title_fullStr Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title_full_unstemmed Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title_short Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
title_sort full population results from the core phase of compleement-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505291/
https://www.ncbi.nlm.nih.gov/pubmed/34414532
http://dx.doi.org/10.1007/s10549-021-06334-0
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