TY - JOUR
T1 - Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study
AU - Yardley, Denise A.
AU - Hart, Lowell
AU - Favret, Anne
AU - Blau, S.
AU - Diab, Sami
AU - Richards, Donald
AU - Sparano, Joseph
AU - Beck, J. Thad
AU - Richards, Paul
AU - Ward, Patrick
AU - Ramaswamy, Bhuvaneswari
AU - Tsai, Michaela
AU - Blackwell, Kimberly
AU - Pluard, Timothy
AU - Tolaney, Sara M.
AU - Esteva, Francisco J.
AU - Truica, Cristina I.
AU - Alemany, Carlos
AU - Volas-Redd, Gena
AU - Shtivelband, Mikhail
AU - Purkayastha, Das
AU - Dalal, Anand A.
AU - Miller, Michelle
AU - Hortobagyi, Gabriel N.
N1 - Funding Information:
D.A. Yardley, L. Hart, A. Favret, S. Diab, D. Richards, J.T. Beck, P. Richards, P. Ward, M. Tsai, and T. Pluard have received research support from Novartis Pharmaceuticals Corporation. D.A. Yardley has received grant support outside of the supported work from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Biomarin, Biothera Pharmaceuticals, Bristol-Myers Squibb, Celgene, Celldex, Clovis, Concordia, Eli Lilly, Eisai, Exelixis, G1 Therapeutics, Genzyme, GlaxoSmithKline, Imclone, Incyte, Ipsen Pharmaceuticals, Janssen, MedImmune, Medivation, Merck, Merrimack Pharmaceuticals, Novartis, Pfizer, Roche/Genentech, Sanofi, Spectrum Pharmaceuticals, and Tesaro; and has received consulting fees outside of the supported work from Abraxis, bioTheranostics, Celgene, Daiichi Sankyo, Eisai, Eli Lilly, ELM Medical Limited, Merck, Nippon-Kayaku, Novartis, Pfizer, R-Pharm US, Roche/Genentech, and Spectrum Pharmaceuticals. B. Ramaswamy has received research support from Novartis Pharmaceuticals Corporation and Pfizer and has received an honorarium for serving on an academic advisory board for Pfizer. S. Blau has received research support from Novartis Pharmaceuticals Corporation and consulting fees from Bristol-Myers Squibb. J. Sparano has received research support from Novartis Pharmaceuticals Corporation and PreCOG, LLC. K. Blackwell has received research support from Novartis Pharmaceuticals Corporation, Celgene, Genentech, and Pfizer, and fees from Novartis Pharmaceutical Corporation, Advaxis, Amgen, AstraZeneca, Bayer, Celgene, Coherus Biosciences, Eisai, Eli Lilly and Company, Genentech, Hospira, Incyte, GI Therapeutics, MacroGenics, Merck, Pfizer, Pierian Biosciences, Puma, Roche, Sandoz, Syndax, and Mylan. S.M. Tolaney has received research support from Novartis Pharmaceuticals Corporation, Pfizer, Nektar, Eli Lilly and Company, Genentech, Merck, AstraZeneca, Bristol-Meyers Squibb, Eisai, and Exelixis, and has served as an advisor to Novartis, Merck, Pfizer, Nektar, Eli Lilly, Genentech, AstraZeneca, Nanostring, and Puma. F.J. Esteva has received research support from Novartis Pharmaceuticals Corporation and consulting fees from Novartis Pharmaceuticals Corporation, Pfizer, Genentech, and Roche. C.I. Truica has received research support and consulting fees from Novartis Pharmaceuticals Corporation. C. Alemany has participated in a speakers bureau for Alexion. G. Volas-Redd has received consulting fees from Novartis Pharmaceuticals Corporation and Pfizer. D. Purkayastha, A.A. Dalal, and M. Miller are paid employees of Novartis Pharmaceuticals Corporation. G.N. Hortobagyi has received research support from Novartis Pharmaceuticals Corporation and consulting fees from Peregrine Pharmaceuticals, Eli Lilly and Company, and Roche. M. Shtivelband has stated no conflicts of interest.Ribociclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals. Editorial assistance was provided under the direction of the authors by Jonathan Morgan, PhD, and Sherri Damlo, MedThink SciCom (Cary, NC), with support from Novartis Pharmaceuticals Corporation. This work was supported by Novartis Pharmaceutical Corporation. The funder of the study had a role in the study design, data collection, data analysis, data interpretation, and writing of the report. All authors had full access to the data and are responsible for the accuracy and completeness of this report. The corresponding author had final responsibility for the decision to submit for publication.
Funding Information:
This work was supported by Novartis Pharmaceutical Corporation. The funder of the study had a role in the study design, data collection, data analysis, data interpretation, and writing of the report. All authors had full access to the data and are responsible for the accuracy and completeness of this report. The corresponding author had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2019
PY - 2019/8
Y1 - 2019/8
N2 - Background: In the Mammary Oncology Assessment of LEE011’s (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR+/HER2− advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2. Patients and Methods: Postmenopausal women with HR+/HER2− ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.5 mg/d (continuous) or placebo with letrozole. The primary end point was locally assessed PFS. Results: Overall, 213 US patients were enrolled in MONALEESA-2 (ribociclib, n = 100; placebo, n = 113). Baseline characteristics were similar between treatment groups and consistent with the global population. With a median follow-up of 27 months, 38 (38%) and 29 (26%) patients in the ribociclib and placebo groups, respectively, had continued to receive treatment. Median PFS was 27.6 months with ribociclib and 15.0 months with placebo (hazard ratio, 0.53). The most common all-cause adverse events were neutropenia (ribociclib, 72.0% [n = 72]; placebo, 4.6% [n = 5]), nausea (ribociclib, 69.0% [n = 69]; placebo, 44.0% [n = 48]), and fatigue (ribociclib, 60.0% [n = 60]; placebo, 50.5% [n = 55]). Two patients (ribociclib, 2.0%; placebo, 0%) experienced febrile neutropenia. Conclusion: In the US subset of MONALEESA-2, ribociclib with letrozole showed superior efficacy versus letrozole alone. These findings are consistent with the global population and support first-line use of ribociclib with letrozole in patients with HR+/HER2− ABC. Endocrine therapy is standard care for postmenopausal women with hormone receptor-positive (HR+)/HER2− advanced breast cancer (ABC). A Mammary Oncology Assessment of LEE011’s (Ribociclib's) Efficacy and Safety (MONALEESA-2) study subset of postmenopausal women with HR+/HER2− ABC without previous treatment for advanced disease were randomized to ribociclib/letrozole or placebo/letrozole. Improved progression-free survival was observed in patients treated with first-line ribociclib/letrozole versus placebo/letrozole, consistent with the global population. These results suggest ribociclib/letrozole is safe and effective in this patient population.
AB - Background: In the Mammary Oncology Assessment of LEE011’s (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR+/HER2− advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2. Patients and Methods: Postmenopausal women with HR+/HER2− ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.5 mg/d (continuous) or placebo with letrozole. The primary end point was locally assessed PFS. Results: Overall, 213 US patients were enrolled in MONALEESA-2 (ribociclib, n = 100; placebo, n = 113). Baseline characteristics were similar between treatment groups and consistent with the global population. With a median follow-up of 27 months, 38 (38%) and 29 (26%) patients in the ribociclib and placebo groups, respectively, had continued to receive treatment. Median PFS was 27.6 months with ribociclib and 15.0 months with placebo (hazard ratio, 0.53). The most common all-cause adverse events were neutropenia (ribociclib, 72.0% [n = 72]; placebo, 4.6% [n = 5]), nausea (ribociclib, 69.0% [n = 69]; placebo, 44.0% [n = 48]), and fatigue (ribociclib, 60.0% [n = 60]; placebo, 50.5% [n = 55]). Two patients (ribociclib, 2.0%; placebo, 0%) experienced febrile neutropenia. Conclusion: In the US subset of MONALEESA-2, ribociclib with letrozole showed superior efficacy versus letrozole alone. These findings are consistent with the global population and support first-line use of ribociclib with letrozole in patients with HR+/HER2− ABC. Endocrine therapy is standard care for postmenopausal women with hormone receptor-positive (HR+)/HER2− advanced breast cancer (ABC). A Mammary Oncology Assessment of LEE011’s (Ribociclib's) Efficacy and Safety (MONALEESA-2) study subset of postmenopausal women with HR+/HER2− ABC without previous treatment for advanced disease were randomized to ribociclib/letrozole or placebo/letrozole. Improved progression-free survival was observed in patients treated with first-line ribociclib/letrozole versus placebo/letrozole, consistent with the global population. These results suggest ribociclib/letrozole is safe and effective in this patient population.
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U2 - 10.1016/j.clbc.2019.02.007
DO - 10.1016/j.clbc.2019.02.007
M3 - Article
C2 - 31160171
AN - SCOPUS:85066308000
SN - 1526-8209
VL - 19
SP - 268-277.e1
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
IS - 4
ER -