Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

Gabe S. Sonke; Lowell L. Hart; Mario Campone; Frans Erdkamp; Wolfgang Janni; Sunil Verma; Cristian Villanueva; Erik Jakobsen; Emilio Alba; Erik Wist; Anne M. Favret; Thomas Bachelot; Roberto Hegg; Paul Wheatley-Price; Farida Souami; Santosh Sutradhar; Michelle Miller; Caroline Germa; Howard A. Burris

doi:10.1007/s10549-017-4523-y

Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

Gabe S. Sonke^*
, Lowell L. Hart
, Mario Campone
, Frans Erdkamp
, Wolfgang Janni
, Sunil Verma
, Cristian Villanueva
, Erik Jakobsen
, Emilio Alba
, Erik Wist
, Anne M. Favret
, Thomas Bachelot
, Roberto Hegg
, Paul Wheatley-Price
, Farida Souami
, Santosh Sutradhar
, Michelle Miller
, Caroline Germa
, Howard A. Burris

^*Kontaktforfatter

The Netherlands Cancer Institute
Florida Cancer Specialists & Research Institute
Sarah Cannon Research Institute
North Laennec Hospital
Sittard-Geleen/Heerlen
University Hospital Ulm
Tom Baker Cancer Centre
University Hospital of Besançon
The Biomedical Research Institute of Malaga
Oslo University Hospital
Virginia Cancer Specialists
The Léon Bérard Cancer Center
Hospital Pérola Byington Centro de Referência da Saúde da Mulher
Ottawa Hospital Research Institute
Novartis
Novartis Pharmaceuticals Corporation
Syddansk Universitet

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.

METHODS: 668 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); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.

RESULTS: Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.

CONCLUSIONS: Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

Originalsprog	Engelsk
Tidsskrift	Breast Cancer Research and Treatment
Vol/bind	167
Udgave nummer	3
Sider (fra-til)	659-669
ISSN	0167-6806
DOI	https://doi.org/10.1007/s10549-017-4523-y
Status	Udgivet - feb. 2018
Udgivet eksternt	Ja

Finansiering

ALT alanine aminotransferase, AST aspartate aminotransferase, UTI urinary tract infection aFour patients in the placebo plus letrozole arm did not receive study treatment bNeutropenia also includes ‘neutrophil count decreased’ and ‘granulocytopenia’ cLeukopenia also includes ‘white blood cell count decreased’ dAnemia also includes ‘anemia macrocytic’ and ‘hemoglobin decreased’ eRash includes ‘maculopapular rash’ fUTI includes ‘cystitis’ and ‘escherichia UTI’ gLiver enzyme elevation includes increases in ALT, AST, and bilirubin levels Acknowledgements We thank all patients and the medical teams of the institutions that participated in the trial, as well as all study steering committee members. Editorial assistance was provided by Jenny Winstanley, Ph.D. (Articulate Science Ltd.) and funded by Novartis Pharmaceuticals Corporation. Ribociclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals. reports research grants and/or honoraria from Sanofi-Aventis, Novartis, Roche, Pfizer, AstraZeneca, Chugai, GSK, Eisai, Celgene, and Johnson & Johnson outside the submitted work. Dr. Alba reports grants from Roche outside the submitted work. Dr. Wist reports personal fees from Novartis for an advisory board and a lecture outside the submitted work. Dr. Bachelot reports grants, personal fees, and non-financial support from Roche, Novartis, and Pfizer and grants and personal fees from AstraZeneca outside the submitted work. Dr. Wheatley-Price reports advisory board fees from Novartis outside the submitted work. Ms. Souami, Dr. Miller, and Dr. Germa are employees of Novartis Pharmaceutical Corporation and hold Novartis stock options. Mr. Sutradhar is an employee of Novartis Pharmaceutical Corporation. Dr. Erdkamp, Dr. Verma, Dr. Villanueva, Dr. Jakobsen, Dr. Favret, Dr. Hegg, and Dr. Burris have nothing to disclose.

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10.1007/s10549-017-4523-yLicens: CC BY

Sonke2018_Article_RibociclibWithLetrozoleVsLetroForlagets udgivne version, 698 KBLicens: CC BY

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Citationsformater

Sonke, G. S., Hart, L. L., Campone, M., Erdkamp, F., Janni, W., Verma, S., Villanueva, C., Jakobsen, E., Alba, E., Wist, E., Favret, A. M., Bachelot, T., Hegg, R., Wheatley-Price, P., Souami, F., Sutradhar, S., Miller, M., Germa, C., & Burris, H. A. (2018). Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Research and Treatment, 167(3), 659-669. https://doi.org/10.1007/s10549-017-4523-y

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title = "Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial",

abstract = "PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.METHODS: 668 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); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.RESULTS: Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95\% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95\% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10\% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10\% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.CONCLUSIONS: Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.",

keywords = "Breast cancer, CDK inhibitor, Elderly, Endocrine therapy, Hormone receptor-positive, Ribociclib, Nitriles/administration \& dosage, Receptors, Progesterone/genetics, Aminopyridines/administration \& dosage, Triazoles/administration \& dosage, Humans, Middle Aged, Receptor, ErbB-2/genetics, Purines/administration \& dosage, Biomarkers, Tumor/genetics, Disease-Free Survival, Aged, 80 and over, Female, Aged, Antineoplastic Combined Chemotherapy Protocols/administration \& dosage, Breast Neoplasms/drug therapy, Letrozole, Receptors, Estrogen/genetics",

author = "Sonke, \{Gabe S.\} and Hart, \{Lowell L.\} and Mario Campone and Frans Erdkamp and Wolfgang Janni and Sunil Verma and Cristian Villanueva and Erik Jakobsen and Emilio Alba and Erik Wist and Favret, \{Anne M.\} and Thomas Bachelot and Roberto Hegg and Paul Wheatley-Price and Farida Souami and Santosh Sutradhar and Michelle Miller and Caroline Germa and Burris, \{Howard A.\}",

year = "2018",

month = feb,

doi = "10.1007/s10549-017-4523-y",

language = "English",

volume = "167",

pages = "659--669",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "3",

}

Sonke, GS, Hart, LL, Campone, M, Erdkamp, F, Janni, W, Verma, S, Villanueva, C, Jakobsen, E, Alba, E, Wist, E, Favret, AM, Bachelot, T, Hegg, R, Wheatley-Price, P, Souami, F, Sutradhar, S, Miller, M, Germa, C & Burris, HA 2018, 'Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial', Breast Cancer Research and Treatment, bind 167, nr. 3, s. 659-669. https://doi.org/10.1007/s10549-017-4523-y

Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. / Sonke, Gabe S.; Hart, Lowell L.; Campone, Mario et al.
I: Breast Cancer Research and Treatment, Bind 167, Nr. 3, 02.2018, s. 659-669.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

AU - Sonke, Gabe S.

AU - Hart, Lowell L.

AU - Campone, Mario

AU - Erdkamp, Frans

AU - Janni, Wolfgang

AU - Verma, Sunil

AU - Villanueva, Cristian

AU - Jakobsen, Erik

AU - Alba, Emilio

AU - Wist, Erik

AU - Favret, Anne M.

AU - Bachelot, Thomas

AU - Hegg, Roberto

AU - Wheatley-Price, Paul

AU - Souami, Farida

AU - Sutradhar, Santosh

AU - Miller, Michelle

AU - Germa, Caroline

AU - Burris, Howard A.

PY - 2018/2

Y1 - 2018/2

N2 - PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.METHODS: 668 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); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.RESULTS: Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.CONCLUSIONS: Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

AB - PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.METHODS: 668 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); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.RESULTS: Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.CONCLUSIONS: Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

KW - Breast cancer

KW - CDK inhibitor

KW - Elderly

KW - Endocrine therapy

KW - Hormone receptor-positive

KW - Ribociclib

KW - Nitriles/administration & dosage

KW - Receptors, Progesterone/genetics

KW - Aminopyridines/administration & dosage

KW - Triazoles/administration & dosage

KW - Humans

KW - Middle Aged

KW - Receptor, ErbB-2/genetics

KW - Purines/administration & dosage

KW - Biomarkers, Tumor/genetics

KW - Disease-Free Survival

KW - Aged, 80 and over

KW - Female

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage

KW - Breast Neoplasms/drug therapy

KW - Letrozole

KW - Receptors, Estrogen/genetics

U2 - 10.1007/s10549-017-4523-y

DO - 10.1007/s10549-017-4523-y

M3 - Journal article

C2 - 29058175

AN - SCOPUS:85031902917

SN - 0167-6806

VL - 167

SP - 659

EP - 669

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -

Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

Abstract

Finansiering

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Fingeraftryk

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