Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.
Slamon, Dennis J.; Neven, Patrick; Chia, Stephenet al.
2018 • In Journal of Clinical Oncology, p. 2018789909
[en] Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naive or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naive in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in >/= 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in >/= 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.
Disciplines :
Oncology
Author, co-author :
Slamon, Dennis J.
Neven, Patrick
Chia, Stephen
Fasching, Peter A.
De Laurentiis, Michelino
Im, Seock-Ah
Petrakova, Katarina
Bianchi, Giulia Val
Esteva, Francisco J.
Martin, Miguel
Nusch, Arnd
Sonke, Gabe S.
De la Cruz-Merino, Luis
Beck, J. Thaddeus
Pivot, Xavier
Vidam, Gena
Wang, Yingbo
Rodriguez Lorenc, Karen
Miller, Michelle
Taran, Tetiana
Jerusalem, Guy ; Université de Liège - ULiège > Département des sciences cliniques > Oncologie
Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.
Publication date :
2018
Journal title :
Journal of Clinical Oncology
ISSN :
0732-183X
eISSN :
1527-7755
Publisher :
American Society of Clinical Oncology, United States - Virginia
Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature 490:61-70, 2012
Thangavel C, Dean JL, Ertel A, et al: Therapeutically activating RB: Reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer 18:333-345, 2011
Finn RS, Dering J, Conklin D, et al: PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 11:R77, 2009
Kim S, Loo A, Chopra R, et al: LEE011: An orally bioavailable, selective small molecule inhibitor of CDK4/6-reactivating rb in cancer. Mol Cancer Ther 12, 2013 (suppl; abstr PR02)
O'Brien N, Di Tomaso E, Ayala R, et al: In vivo efficacy of combined targeting of CDK4/6, ER and PI3K signaling in ER+ breast cancer. Presented at American Association for Cancer Research Annual Meeting, San Diego, CA, April 5-9, 2014 (abstr 4756)
Hortobagyi GN, Stemmer SM, Burris HA, et al: Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375:1738-1748, 2016
Tripathy D, Sohn J, Im SA, et al: First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. Presented at San Antonio Breast Cancer Symposium, San Antonio, TX, December 5-9, 2017 (abstr GS2-05)
Turner NC, Ro J, André F, et al: Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med 373:209-219, 2015
Cristofanilli M, Turner NC, Bondarenko I, et al: Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): Final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17: 425-439, 2016
Sledge GW Jr, Toi M, Neven P, et al: MONARCH 2: Abemaciclib in combination with fulvestrant inwomenwithHR+, HER22advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35:2875-2884, 2017
Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009
National Cancer Institute Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse Events (CTCAE) v4.0. http://Ctep.cancer. gov/protocolDevelopment/electronic-applications/ ctc.htm
Hortobagyi GN, Stemmer SM, Burris HA, et al: Updated results from MONALEESA-2, a phase III trial of first-line ribociclib + letrozole in hormone receptorpositive, HER2-negative advanced breast cancer. J Clin Oncol 35, 2017 (suppl; abstr 1038)
Robertson JFR, Bondarenko IM, Trishkina E, et al: Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): An international, randomised, doubleblind, phase 3 trial. Lancet 388:2997-3005, 2016
