nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F21%3A00078808" target="_blank" >RIV/00209805:_____/21:00078808 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.clinicalkey.com/service/content/pdf/watermarked/1-s2.0-S152682092030255X.pdf?locale=en_US&searchIndex=" target="_blank" >https://www.clinicalkey.com/service/content/pdf/watermarked/1-s2.0-S152682092030255X.pdf?locale=en_US&searchIndex=</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.clbc.2020.09.011" target="_blank" >10.1016/j.clbc.2020.09.011</a>

Jazyk výsledku

angličtina

Název v původním jazyce

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Popis výsledku v původním jazyce

nextMONARCH investigated abemaciclib monotherapy and abemaciclib combined with tamoxifen. Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) were treated with abemaciclib (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory MBC after chemotherapy. The results confirmed the single-agent activity of abemaciclib in heavily pretreated hormone receptor-positive, human epidermal growth factor receptor 2-negative MBC. Background: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR*), human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. Patients and Methods: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2(-) MBC previously treated with chemoherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. Results: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence nterval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. Conclusions: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2(-) MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy. (C) 2020 Published by Elsevier Inc.

Název v anglickém jazyce

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Popis výsledku anglicky

nextMONARCH investigated abemaciclib monotherapy and abemaciclib combined with tamoxifen. Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) were treated with abemaciclib (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory MBC after chemotherapy. The results confirmed the single-agent activity of abemaciclib in heavily pretreated hormone receptor-positive, human epidermal growth factor receptor 2-negative MBC. Background: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR*), human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy. Patients and Methods: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2(-) MBC previously treated with chemoherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics. Results: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence nterval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations. Conclusions: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2(-) MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy. (C) 2020 Published by Elsevier Inc.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

CLINICAL BREAST CANCER

ISSN

1526-8209

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

181-"190.e2"

Kód UT WoS článku

000663349200026

EID výsledku v databázi Scopus

2-s2.0-85096402456