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

Mario Campone, Seock Ah Im, Hiroji Iwata, Mark Clemons, Yoshinori Ito, Ahmad Awada, Stephen Chia, Agnieszka Jagiełło-Gruszfeld, Barbara Pistilli, Ling Ming Tseng, Sara Hurvitz, Norikazu Masuda, Javier Cortés, Michele De Laurentiis, Carlos L. Arteaga, Zefei Jiang, Walter Jonat, Sylvie Le Mouhaër, Banu Sankaran, Laurence BourdeauMona El-Hashimy, Dalila Sellami, José Baselga

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalEuropean Journal of Cancer
Volume103
DOIs
StatePublished - Nov 1 2018

Fingerprint

Placebos
Phosphatidylinositol 3-Kinase
Hormones
Breast Neoplasms
Survival
Disease-Free Survival
DNA
Neoplasms
NVP-BKM120
human ERBB2 protein
fulvestrant
Random Allocation
Aspartate Aminotransferases
Alanine Transaminase
Hyperglycemia
Population
Safety

Keywords

  • Buparlisib
  • ctDNA
  • Fulvestrant
  • Hormone receptor-positive breast cancer
  • Overall survival
  • PIK3CA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Campone, Mario; Im, Seock Ah; Iwata, Hiroji; Clemons, Mark; Ito, Yoshinori; Awada, Ahmad; Chia, Stephen; Jagiełło-Gruszfeld, Agnieszka; Pistilli, Barbara; Tseng, Ling Ming; Hurvitz, Sara; Masuda, Norikazu; Cortés, Javier; De Laurentiis, Michele; Arteaga, Carlos L.; Jiang, Zefei; Jonat, Walter; Le Mouhaër, Sylvie; Sankaran, Banu; Bourdeau, Laurence; El-Hashimy, Mona; Sellami, Dalila; Baselga, José.

In: European Journal of Cancer, Vol. 103, 01.11.2018, p. 147-154.

Research output: Contribution to journalArticle

Campone, M, Im, SA, Iwata, H, Clemons, M, Ito, Y, Awada, A, Chia, S, Jagiełło-Gruszfeld, A, Pistilli, B, Tseng, LM, Hurvitz, S, Masuda, N, Cortés, J, De Laurentiis, M, Arteaga, CL, Jiang, Z, Jonat, W, Le Mouhaër, S, Sankaran, B, Bourdeau, L, El-Hashimy, M, Sellami, D & Baselga, J 2018, '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', European Journal of Cancer, vol. 103, pp. 147-154. https://doi.org/10.1016/j.ejca.2018.08.002
Campone, Mario ; Im, Seock Ah ; Iwata, Hiroji ; Clemons, Mark ; Ito, Yoshinori ; Awada, Ahmad ; Chia, Stephen ; Jagiełło-Gruszfeld, Agnieszka ; Pistilli, Barbara ; Tseng, Ling Ming ; Hurvitz, Sara ; Masuda, Norikazu ; Cortés, Javier ; De Laurentiis, Michele ; Arteaga, Carlos L. ; Jiang, Zefei ; Jonat, Walter ; Le Mouhaër, Sylvie ; Sankaran, Banu ; Bourdeau, Laurence ; El-Hashimy, Mona ; Sellami, Dalila ; Baselga, José. / 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. In: European Journal of Cancer. 2018 ; Vol. 103. pp. 147-154.
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abstract = "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.",
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TY - JOUR

T1 - Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer

T2 - Overall survival results from BELLE-2

AU - Campone, Mario

AU - Im, Seock Ah

AU - Iwata, Hiroji

AU - Clemons, Mark

AU - Ito, Yoshinori

AU - Awada, Ahmad

AU - Chia, Stephen

AU - Jagiełło-Gruszfeld, Agnieszka

AU - Pistilli, Barbara

AU - Tseng, Ling Ming

AU - Hurvitz, Sara

AU - Masuda, Norikazu

AU - Cortés, Javier

AU - De Laurentiis, Michele

AU - Arteaga, Carlos L.

AU - Jiang, Zefei

AU - Jonat, Walter

AU - Le Mouhaër, Sylvie

AU - Sankaran, Banu

AU - Bourdeau, Laurence

AU - El-Hashimy, Mona

AU - Sellami, Dalila

AU - Baselga, José

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

KW - Buparlisib

KW - ctDNA

KW - Fulvestrant

KW - Hormone receptor-positive breast cancer

KW - Overall survival

KW - PIK3CA

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