Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†

M. Piccart, G. N. Hortobagyi, M. Campone, K. I. Pritchard, F. Lebrun, Y. Ito, S. Noguchi, Alejandra Perez, H. S. Rugo, I. Deleu, H. A. Burris, L. Provencher, P. Neven, M. Gnant, M. Shtivelband, C. Wu, J. Fan, W. Feng, T. Taran, J. Baselga

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.

PATIENTS AND METHODS: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.

RESULTS: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.

CONCLUSIONS: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P <0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.

TRIAL REGISTRATION NUMBER: NCT00863655.

Original languageEnglish (US)
Pages (from-to)2357-2362
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

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exemestane
Hormones
Breast Neoplasms
Survival
Disease-Free Survival
Placebos
Aromatase Inhibitors
Confidence Intervals
Everolimus
human ERBB2 protein
Therapeutics

Keywords

  • everolimus
  • exemestane
  • hormone-receptor-positive breast cancer
  • overall survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer : overall survival results from BOLERO-2†. / Piccart, M.; Hortobagyi, G. N.; Campone, M.; Pritchard, K. I.; Lebrun, F.; Ito, Y.; Noguchi, S.; Perez, Alejandra; Rugo, H. S.; Deleu, I.; Burris, H. A.; Provencher, L.; Neven, P.; Gnant, M.; Shtivelband, M.; Wu, C.; Fan, J.; Feng, W.; Taran, T.; Baselga, J.

In: Annals of Oncology, Vol. 25, No. 12, 01.12.2014, p. 2357-2362.

Research output: Contribution to journalArticle

Piccart, M, Hortobagyi, GN, Campone, M, Pritchard, KI, Lebrun, F, Ito, Y, Noguchi, S, Perez, A, Rugo, HS, Deleu, I, Burris, HA, Provencher, L, Neven, P, Gnant, M, Shtivelband, M, Wu, C, Fan, J, Feng, W, Taran, T & Baselga, J 2014, 'Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†', Annals of Oncology, vol. 25, no. 12, pp. 2357-2362. https://doi.org/10.1093/annonc/mdu456
Piccart, M. ; Hortobagyi, G. N. ; Campone, M. ; Pritchard, K. I. ; Lebrun, F. ; Ito, Y. ; Noguchi, S. ; Perez, Alejandra ; Rugo, H. S. ; Deleu, I. ; Burris, H. A. ; Provencher, L. ; Neven, P. ; Gnant, M. ; Shtivelband, M. ; Wu, C. ; Fan, J. ; Feng, W. ; Taran, T. ; Baselga, J. / Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer : overall survival results from BOLERO-2†. In: Annals of Oncology. 2014 ; Vol. 25, No. 12. pp. 2357-2362.
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abstract = "BACKGROUND: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.PATIENTS AND METHODS: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.RESULTS: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95{\%} confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95{\%} CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95{\%} CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84{\%} of patients in the EVE + EXE arm versus 90{\%} of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53{\%} EVE + EXE versus 63{\%} PBO + EXE). No new safety concerns were identified.CONCLUSIONS: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P <0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.TRIAL REGISTRATION NUMBER: NCT00863655.",
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TY - JOUR

T1 - Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer

T2 - overall survival results from BOLERO-2†

AU - Piccart, M.

AU - Hortobagyi, G. N.

AU - Campone, M.

AU - Pritchard, K. I.

AU - Lebrun, F.

AU - Ito, Y.

AU - Noguchi, S.

AU - Perez, Alejandra

AU - Rugo, H. S.

AU - Deleu, I.

AU - Burris, H. A.

AU - Provencher, L.

AU - Neven, P.

AU - Gnant, M.

AU - Shtivelband, M.

AU - Wu, C.

AU - Fan, J.

AU - Feng, W.

AU - Taran, T.

AU - Baselga, J.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - BACKGROUND: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.PATIENTS AND METHODS: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.RESULTS: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.CONCLUSIONS: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P <0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.TRIAL REGISTRATION NUMBER: NCT00863655.

AB - BACKGROUND: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.PATIENTS AND METHODS: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.RESULTS: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.CONCLUSIONS: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P <0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.TRIAL REGISTRATION NUMBER: NCT00863655.

KW - everolimus

KW - exemestane

KW - hormone-receptor-positive breast cancer

KW - overall survival

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DO - 10.1093/annonc/mdu456

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VL - 25

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JO - Annals of Oncology

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