Abstract
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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Breast CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Estimation of the number of women living with metastatic breast cancer in the United States.Cancer Epidemiol Biomarkers Prev. 2017; 26: 809-815
- Cancer Facts & Figures 2018.(Available at:)
- Goals and objectives in the management of metastatic breast cancer.Oncologist. 2003; 8: 514-520
- Goals of treatment for patients with metastatic breast cancer.Semin Oncol. 2006; 33: 2-5
- NCCN Clinical Practice Guidelines in Oncology.(Available at:)https://www.nccn.org/professionals/physician_gls/pdf/breast_blocks.pdfDate accessed: August 28, 2018
- Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline.J Clin Oncol. 2016; 34: 3069-3103
- Phase III study of letrozole vs. tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.J Clin Oncol. 2003; 21: 2101-2109
- Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial.J Clin Oncol. 2000; 18: 3758-3767
- Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women.J Clin Oncol. 2008; 26: 4883-4890
- Palbociclib and letrozole in advanced breast cancer.N Engl J Med. 2016; 375: 1925-1936
- Updated results from MONALEESA-2, a phase III trial of first-line ribociclib + letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.(Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 2-6)2017
- MONARCH 3: abemaciclib as initial therapy for advanced breast cancer.J Clin Oncol. 2017; 35: 3638-3646
- Kisqali (ribociclib) Tablets [prescribing information]. Novartis Pharmaceuticals Corp, East Hanover, NJ2018
- Ibrance (palbociclib) Capsules [prescribing information]. Pfizer Inc, New York, NY2018
- Verzenio (abemaciclib) [prescribing information]. Eli Lilly and Company, Indianapolis, IN2018
- Ribociclib as first-line therapy for HR-positive, advanced breast cancer.N Engl J Med. 2016; 375: 1738-1748
- New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).Eur J Cancer. 2009; 45: 228-247
- Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin Oncol. 1982; 5: 649-656
- The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.J Natl Cancer Inst. 1993; 85: 365-376
- Common terminology criteria for adverse events (CTCAE), version 4.0.(Available at:)http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htmDate accessed: August 28, 2018
- Streamlining adverse events reporting in oncology: an American Society of Clinical Oncology research statement.J Clin Oncol. 2018; 36: 617-623
- Interpreting geographic variations in results of randomized, controlled trials.N Engl J Med. 2016; 375: 2263-2271
- How to promote adverse drug reaction reports using information systems–a systematic review and meta-analysis.BMC Med Inform Decis Mak. 2016; 16: 27
- Reporting clinical end points and safety events in an acute coronary syndrome trial: results with integrated collection.J Am Heart Assoc. 2017; 6: e005490
- Cross-cultural evaluation of health status using item response theory: FACT-B comparisons between Austrian and US patients with breast cancer.Eval Health Prof. 2005; 28: 233-259
- Health-related quality of life in breast cancer: a cross-cultural survey of German, Japanese, and South Korean patients.Breast Cancer Res Treat. 2006; 99: 341-350
- Efficacy and safety of palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: findings by geographic region from PALOMA-2.(Presented at the 40th Annual San Antonio Breast Cancer Symposium; San Antonio, TX; Dec 5-9)2017
- 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 Res Treat. 2018; 167: 659-669
- Ribociclib plus letrozole vs. letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial.Breast Cancer Res Treat. 2018; 168: 127-134
- Fulvestrant plus palbociclib vs. 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. 2016; 17: 425-439
- MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy.J Clin Oncol. 2017; 35: 2875-2884
Article info
Publication history
Published online: February 27, 2019
Accepted:
February 15,
2019
Received in revised form:
January 29,
2019
Received:
November 14,
2018
Footnotes
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.
Identification
Copyright
© 2019 Published by Elsevier Inc.
