Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer

Hortobágyi, Gabriel N.; Stemmer, Salomon M.; Burris, Howard A.; Yap, Yoon Sim; Sonke, Gabe S.; Paluch‐Shimon, Shani; Campone, Mario; Petráková, Katarína; Blackwell, Kimberly; Winer, Eric P.; Janni, Wolfgang; Verma, S.; Conté, Pierfranco; Arteaga, Carlos L.; Cameron, David; Mondal, Shoubhik; Su, Fei; Miller, Michelle C.; Elmeliegy, Mohamed; Germa, Caroline; O’Shaughnessy, Joyce

doi:10.1093/annonc/mdy155

Cited by 555 publications

(434 citation statements)

References 10 publications

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“…At a median follow-up of 26.4 months, an improvement in PFS (25.3 vs 16.0 months; HR for progression or death was 0.56; 95% CI, 0.45-0.70) and improved ORR of 43% vs 29% was seen with ribociclib plus letrozole compared with letrozole alone. 29 Grade 3 or 4 adverse events were more common with the combination, including neutropenia (62% vs 1.2%), leukopenia (21.3% vs 0.9%), and abnormal liver function tests (10.2% vs 2.4%). 29 The phase III MONARCH trial studied the combination of abemaciclib either with an AI (letrozole or anastrozole) versus AI monotherapy as first-line treatment of women with advanced HR-positive, HER2-negative breast cancer.…”

Section: Systemic Therapy For Stage IV or Recurrent Metastatic Hr-posmentioning

confidence: 94%

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Gradishar

Anderson

Abraham

et al. 2020

Journal of the National Comprehensive Cancer Network

962

599

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Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

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Section: Systemic Therapy For Stage IV or Recurrent Metastatic Hr-posmentioning

confidence: 94%

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Gradishar

Anderson

Abraham

et al. 2020

Journal of the National Comprehensive Cancer Network

962

599

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“…The compound has been approved by a number of health authorities, including the United States Food and Drug Administration (US FDA) and the European Medicines Agency, for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor (AI) or fulvestrant. 1,2,3 Additional marketing authorizations are under review by health authorities worldwide.…”

Section: Introductionmentioning

confidence: 99%

An integrated assessment of the ADME properties of the CDK4/6 Inhibitor ribociclib utilizing preclinical in vitro, in vivo, and human ADME data

James

Schiller

Marvalin

et al. 2020

Pharmacology Res & Perspec

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Ribociclib (LEE011, Kisqali ®) is a highly selective small molecule inhibitor of cyclindependent kinases 4 and 6 (CDK4/6), which has been approved for the treatment of advanced or metastatic breast cancer. A human ADME study was conducted in healthy male volunteers following a single oral dose of 600 mg [ 14 C]-ribociclib. Mass balance, blood and plasma radioactivity, and plasma ribociclib concentrations were measured. Metabolite profiling and identification was conducted in plasma, urine, and feces. An assessment integrating the human ADME results with relevant in vitro and in vivo non-clinical data was conducted to provide an estimate of the relative contributions of various clearance pathways of the compound. Ribociclib is moderately to highly absorbed across species (approx. 59% in human), and is extensively metabolized in vivo, predominantly by oxidative pathways mediated by CYP3A4 (ultimately forming N-demethylated metabolite M4) and, to a lesser extent, by FMO3 (N-hydroxylated metabolite M13). It is extensively distributed in rats, based on QWBA data, and is eliminated rapidly from most tissues with the exception of melanin-containing structures. Ribociclib passed the placental barrier in rats and rabbits and into milk of lactating rats. In human, 69.1% and 22.6% of the radiolabeled dose were excreted in feces and urine, respectively, with 17.3% and 6.75% of the 14 C dose attributable to ribociclib, respectively. The remainder was attributed to numerous metabolites. Taking into account all available data, ribociclib is estimated to be eliminated by hepatic metabolism (approx. 84% of total), renal excretion (7%), intestinal excretion (8%), and biliary elimination (1%). K E Y W O R D SADME, human, Kisquali, preclinical, Ribociclib

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“…This is less than the 10-to 16-month PFS results observed in first-line hormonal therapy control arms in modern-era CDKI trials but similar to the results for the aromatase inhibitor arms in the early aromatase inhibitor versus tamoxifen first-line trials. 9,[18][19][20] Although the CDKI studies reported PFS, this can be considered to be analogous to the duration of treatment because progression usually triggers a change in therapy. Key differences between a trial and a general population likely explain some or all of the PFS differences between our population cohorts and the trial populations.…”

Section: Discussionmentioning

confidence: 99%

The impact of new systemic therapies on survival and time on hormonal treatment in hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer: A population‐based study in British Columbia from 2003 to 2013

Le¹,

Speers

Thompson

et al. 2019

Cancer

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Background The purpose of this study was to determine whether new systemic therapy regimens have resulted in improved survival and increased time on first‐ and second‐line hormonal treatment for patients with hormone receptor (HR)–positive metastatic breast cancer (MBC) over time. Methods Patients diagnosed with HR‐positive, human epidermal growth factor receptor 2 (HER2)–negative MBC were identified across 3 time cohorts (2003‐2005, 2007‐2009, and 2011‐2013). Data were prospectively collected. Cases with previous, synchronous, or subsequent contralateral breast cancer were excluded. The types of first‐ and second‐line therapies, the times on first‐ and second‐line hormonal treatment, and the median survival times were compared across the cohorts. Results Within the time period analyzed, 9 new adjuvant systemic therapies (with or without neoadjuvant therapy) and 2 metastatic systemic therapies were approved at BC Cancer for the treatment of HR‐positive, HER2‐negative MBC. In the 3 time cohorts, 3953 patients diagnosed with MBC were identified. Among the 2432 patients (62%) who had HR‐positive/HER2‐negative disease, 2197 (90%) received at least 1 line of systemic therapy after the diagnosis of MBC, and 80% of these patients (1752 of 2197) received first‐ and/or second‐line hormonal treatment. The median duration on hormonal treatment was 9.0 months for the first line and 6.1 months for the second line. The durations were similar across the time cohorts (range for the first line, 8.9‐9.0 months; range for the second line, 6.0‐6.1 months). The median survival for the entire study population was 2.0 years (95% confidence interval, 1.8‐2.1 years), and there was no significant difference between the cohorts (range, 1.9‐2.0 years). Conclusions Even though more adjuvant and metastatic systemic therapies have been approved since 2003, population‐level gains in survival and the time on hormonal treatment for patients with HR‐positive, HER2‐negative MBC have not been made over the course of a decade.

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Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer

Abstract: NCT01958021.

Cited by 555 publications

References 10 publications

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

An integrated assessment of the ADME properties of the CDK4/6 Inhibitor ribociclib utilizing preclinical in vitro, in vivo, and human ADME data

The impact of new systemic therapies on survival and time on hormonal treatment in hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer: A population‐based study in British Columbia from 2003 to 2013

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