Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2

被引：51

作者：

Campone, Mario ^{[1
]}

Im, Seock-Ah ^{[2
]}

Iwata, Hiroji ^{[3
]}

Clemons, Mark ^{[4
]}

Ito, Yoshinori ^{[5
]}

Awada, Ahmad ^{[6
]}

Chia, Stephen ^{[7
]}

Jagiello-Gruszfeld, Agnieszka ^{[8
]}

Pistilli, Barbara ^{[9
]}

Tseng, Ling-Ming ^{[10
]}

Hurvitz, Sara ^{[11
]}

Masuda, Norikazu ^{[12
]}

Cortes, Javier ^{[13
,14
]}

De Laurentiis, Michele ^{[15
]}

Arteaga, Carlos L. ^{[16
]}

Jiang, Zefei ^{[17
]}

Jonat, Walter ^{[18
]}

Le Mouhaer, Sylvie ^{[19
]}

Sankaran, Banu ^{[20
]}

Bourdeau, Laurence ^{[19
]}

El-Hashimy, Mona

Sellami, Dalila

Baselga, Jose

机构：

[1] Inst Cancerol Ouest, Ctr Rene Gauducheau, Blvd Jacques Monod, F-44805 St Herblain, France

[2] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Dept Internal Med,Canc Res Inst, Seoul, South Korea

[3] Aichi Canc Ctr, Dept Breast Oncol, Nagoya, Aichi, Japan

[4] Ottawa Hosp Res Inst, Div Med Oncol, Ottawa, ON, Canada

[5] Japanese Fdn Canc Res, Canc Inst Hosp, Breast Oncol Ctr, Tokyo, Japan

[6] Inst Jules Bordet, Med Oncol Clin, Brussels, Belgium

[7] BC Canc Agcy, Med Oncol, Vancouver, BC, Canada

[8] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Ctr Oncol, Warsaw, Poland

[9] Macerata Hosp, Macerata, Italy

[10] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Dept Surg, Taipei, Taiwan

[11] Univ Calif Los Angeles, UCLA Jonsson Comprehens Canc Ctr, Los Angeles, CA USA

[12] Natl Hosp Org Osaka Natl Hosp, Dept Surg & Breast Oncol, Osaka, Japan

[13] Ramon y Cajal Univ Hosp, Inst Oncol, Madrid, Spain

[14] Vall DHebron Inst Oncol VHIO, Breast Canc Res Program, Barcelona, Spain

[15] Fdn G Pascale, Ist Nazl Tumori, Breast Canc Dept, Naples, Italy

[16] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[17] PLA, Beijing Hosp 307, Dept Breast Canc, Beijing, Peoples R China

[18] Univ Hosp Schleswig Holstein, Med Ctr, Kiel, Germany

[19] Novartis Pharma SAS, Paris, France

[20] Novartis Inst BioMed Res, Cambridge, MA USA

来源：

EUROPEAN JOURNAL OF CANCER | 2018年 / 103卷

关键词：

Buparlisib; Fulvestrant; Hormone receptor-positive breast cancer; Overall survival; PIK3CA; ctDNA; INHIBITOR; HETEROGENEITY; RESISTANCE; BKM120; TRIAL;

D O I：

10.1016/j.ejca.2018.08.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus fulvestrant in the BELLE-2 study significantly improved progression-free survival (PFS) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Patients and methods: In this phase III study, patients were randomised 1: 1 to buparlisib (100 mg/day; continuously in 28-day cycles) or placebo, plus fulvestrant (500 mg on cycle 1 day 15, and day 1 of subsequent cycles). Overall survival (OS) was assessed in the overall population and patients with known PI3K pathway status (both had shown significant PFS improvements). OS by PIK3CA status in circulating tumour DNA (ctDNA) was an exploratory end-point. Results: A total of 2025 patients were screened for eligibility between 7th September 2012 and 10th September 2014, and 1178 received fulvestrant (500 mg) during a run-in phase; 31 discontinued. Of 1147 patients (median age 62 years), 98% had the Eastern Cooperative Oncology Group performance status <= 1, and 59% had visceral disease. Median follow-up from randomisation to data cut-off (23rd December 2016) was 37.6 months. Median OS trended in favour of the buparlisib arm in the overall population (33.2 versus 30.4 months; P = 0.045) and among patients with known PI3K pathway status (30.9 versus 28.9 months; P = 0.144); neither outcome was statistically significant. Median OS also trended in favour of buparlisib among patients with PIK3CA-mutant ctDNA (26.0 versus 24.8 months). Grade III/IV adverse events with >= 10% difference between the buparlisib versus placebo arms were elevated alanine aminotransferase (26% versus 1%), elevated aspartate aminotransferase (18% versus 3%) and hyperglycemia (15% versus <1%). Conclusions: OS results were in favour of buparlisib plus fulvestrant versus placebo plus fulvestrant; however, there is no statistical significance and more frequent grade III/IV adverse events were reported. Use of more selective PI3K inhibitors might provide the greatest clinical benefit and tolerable safety profile in this setting. Further evaluation of the predictive benefit of PIK3CA-mutant ctDNA is warranted. Trial registration number: NCT01610284. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：147 / 154

页数：8

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