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.
N1 - Funding Information:
Funding The study was initiated, funded, and sponsored by Novartis Pharmaceuticals Corporation. Design and conduct of the study was undertaken by the sponsor in collaboration with investigators. The study investigators and their respective research teams collected the data; Novartis Pharmaceuticals Corporation compiled the data for summation and analysis. All authors were responsible for data interpretation. The article was prepared by Dr. O’Shaughnessy in conjunction with all the authors, including employees of the sponsor. The corresponding author had final responsibility for the decision to submit the manuscript for publication.
Funding Information:
took part in this study and their families, as well as the staff at each study site, and all study steering committee members. Medical editorial assistance was provided by Jenny Winstanley, PhD (ArticulateScience Ltd.) and was funded by Novartis Pharmaceuticals Corporation. Ribo-ciclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals.
Funding Information:
The authors would like to thank the patients who took part in this study and their families, as well as the staff at each study site, and all study steering committee members. Medical editorial assistance was provided by Jenny Winstanley, PhD (ArticulateScience Ltd.) and was funded by Novartis Pharmaceuticals Corporation. Ribociclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals. The study was initiated, funded, and sponsored by Novartis Pharmaceuticals Corporation. Design and conduct of the study was undertaken by the sponsor in collaboration with investigators. The study investigators and their respective research teams collected the data; Novartis Pharmaceuticals Corporation compiled the data for summation and analysis. All authors were responsible for data interpretation. The article was prepared by Dr. O’Shaughnessy in conjunction with all the authors, including employees of the sponsor. The corresponding author had final responsibility for the decision to submit the manuscript for publication.
Publisher Copyright:
© 2017, The Author(s).
PY - 2018/2/1
Y1 - 2018/2/1
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
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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
SN - 0167-6806
VL - 168
SP - 127
EP - 134
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -