Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

Joyce O’Shaughnessy, Katarina Petrakova, Gabe S. Sonke, Pierfranco Conte, Carlos L. Arteaga, David A. Cameron, Lowell L. Hart, Cristian Villanueva, Erik Jakobsen, Joseph T. Beck, Deborah Lindquist, Farida Souami, Shoubhik Mondal, Caroline Germa, Gabriel N. Hortobagyi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Methods: Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Results: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Conclusions: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Nov 21 2017

Fingerprint

letrozole
Breast Neoplasms
Disease-Free Survival
Placebos
Safety
ribociclib
Leukopenia

Keywords

  • Breast cancer
  • CDK inhibitor
  • De novo advanced breast cancer
  • Endocrine therapy
  • Hormone receptor-positive
  • Ribociclib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial. / O’Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S.; Conte, Pierfranco; Arteaga, Carlos L.; Cameron, David A.; Hart, Lowell L.; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T.; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N.

In: Breast Cancer Research and Treatment, 21.11.2017, p. 1-8.

Research output: Contribution to journalArticle

O’Shaughnessy, J, Petrakova, K, Sonke, GS, Conte, P, Arteaga, CL, Cameron, DA, Hart, LL, Villanueva, C, Jakobsen, E, Beck, JT, Lindquist, D, Souami, F, Mondal, S, Germa, C & Hortobagyi, GN 2017, 'Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial', Breast Cancer Research and Treatment, pp. 1-8. https://doi.org/10.1007/s10549-017-4518-8
O’Shaughnessy, Joyce ; Petrakova, Katarina ; Sonke, Gabe S. ; Conte, Pierfranco ; Arteaga, Carlos L. ; Cameron, David A. ; Hart, Lowell L. ; Villanueva, Cristian ; Jakobsen, Erik ; Beck, Joseph T. ; Lindquist, Deborah ; Souami, Farida ; Mondal, Shoubhik ; Germa, Caroline ; Hortobagyi, Gabriel N. / Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial. In: Breast Cancer Research and Treatment. 2017 ; pp. 1-8.
@article{29bd6672921348469bf4198fda6667bc,
title = "Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial",
abstract = "Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Methods: Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Results: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34{\%}; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95{\%} confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Conclusions: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.",
keywords = "Breast cancer, CDK inhibitor, De novo advanced breast cancer, Endocrine therapy, Hormone receptor-positive, Ribociclib",
author = "Joyce O’Shaughnessy and Katarina Petrakova and Sonke, {Gabe S.} and Pierfranco Conte and Arteaga, {Carlos L.} and Cameron, {David A.} and Hart, {Lowell L.} and Cristian Villanueva and Erik Jakobsen and Beck, {Joseph T.} and Deborah Lindquist and Farida Souami and Shoubhik Mondal and Caroline Germa and Hortobagyi, {Gabriel N.}",
year = "2017",
month = "11",
day = "21",
doi = "10.1007/s10549-017-4518-8",
language = "English (US)",
pages = "1--8",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",

}

TY - JOUR

T1 - Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

AU - O’Shaughnessy, Joyce

AU - Petrakova, Katarina

AU - Sonke, Gabe S.

AU - Conte, Pierfranco

AU - Arteaga, Carlos L.

AU - Cameron, David A.

AU - Hart, Lowell L.

AU - Villanueva, Cristian

AU - Jakobsen, Erik

AU - Beck, Joseph T.

AU - Lindquist, Deborah

AU - Souami, Farida

AU - Mondal, Shoubhik

AU - Germa, Caroline

AU - Hortobagyi, Gabriel N.

PY - 2017/11/21

Y1 - 2017/11/21

N2 - Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Methods: Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Results: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Conclusions: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.

AB - Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Methods: Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Results: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Conclusions: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.

KW - Breast cancer

KW - CDK inhibitor

KW - De novo advanced breast cancer

KW - Endocrine therapy

KW - Hormone receptor-positive

KW - Ribociclib

UR - http://www.scopus.com/inward/record.url?scp=85034667232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034667232&partnerID=8YFLogxK

U2 - 10.1007/s10549-017-4518-8

DO - 10.1007/s10549-017-4518-8

M3 - Article

C2 - 29164421

AN - SCOPUS:85034667232

SP - 1

EP - 8

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

ER -