Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

O’Shaughnessy, Joyce; Petráková, Katarína; Sonke, Gabe S.; Conte, Pierfranco; Arteaga, Carlos L.; Cameron, David; Hart, Lowell L.; Villanueva, Cristian; Jakobsen, Erik; Beck, J. Thaddeus; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobágyi, Gabriel N.

doi:10.1007/s10549-017-4518-8

Cited by 93 publications

(100 citation statements)

References 25 publications

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“…Comparable efficacy has also been demonstrated in the sub‐group with de novo advanced breast cancer in the MONALEESA‐2 study. The median PFS was not reached in the ribociclib plus letrozole arm compared with 16.4 months with letrozole (HR 0.45; 95% CI 0.27 to 0.75) . In addition, ribociclib plus a NSAI also had clinical activity in patients with high burden of disease, and was associated with a lower rate of treatment discontinuation in patients with three or more metastatic sites compared to placebo (45% vs. 60%) …”

Section: Clinical Trial Data: Efficacymentioning

confidence: 97%

Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of CDK4/6 inhibitors on the current treatment paradigm

Boyle

Beith

Burslem³

et al. 2018

Asia-Pac J Clncl Oncology

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Resistance to endocrine therapy is a significant therapeutic challenge in the treatment of women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Cyclin-dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy have been shown to improve progression free survival, overall response rate and clinical benefit rate in women with HR+ HER2-metastatic breast cancer compared with endocrine therapy alone. This review examines the clinical evidence to support the use of CDK4/6 inhibitors in first and second line settings. Practical guidance is provided for the use of CDK4/6 inhibitors, including tolerability data, monitoring requirements and management of key toxicities for each of the available agents. K E Y W O R D S CDK4/6 inhibitor, endocrine therapy, metastatic breast cancer tion of Rb leads to increased DNA replication within the tumor cell and subsequent driving of the cell cycle. Tumor cells are able to avoid senescence through mechanisms such as CDK4 amplification. Consequently, inhibition of CDK4 can lead to senescence. Furthermore, CDK6

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Section: Clinical Trial Data: Efficacymentioning

confidence: 97%

Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of CDK4/6 inhibitors on the current treatment paradigm

Boyle

Beith

Burslem³

et al. 2018

Asia-Pac J Clncl Oncology

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“…Following the results of PALOMA-1, 30 PALOMA-2 31 and PALOMA-3, 32 palbociclib was approved by FDA in the United States and EMA in Europe for the treatment of patients with metastatic BC ER-positive HER2-negative in combination with AIs or fulvestrant. Ribociclib has been approved by the FDA and EMA for the same indications as palbociclib, based on the results of MONALEESA-2, 33 MONALEESA-3 34 and MONALEESA-7. 35 The Phase 3 MONARCH study demonstrated the clinical efficacy and safety of abemaciclib, achieving similar results in combination with AIs and fulvestrant.…”

Section: Er+ Advanced Bc Clinical Data Of Cdk 4/6 Inhibitors In Advanmentioning

confidence: 99%

<p>Strategies for Increasing the Effectiveness of Aromatase Inhibitors in Locally Advanced Breast Cancer: An Evidence-Based Review on Current Options</p>

Grizzi¹,

Ghidini²,

Botticelli³

et al. 2020

CMAR

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Neoadjuvant hormonal therapy (NEO-HT) is a possible treatment option for breast cancer (BC) patient with estrogen receptor positive (ER+) and HER2 negative (HER2-) disease. The absence of solid data on the type of drugs to be used and duration of treatment as well as lack of clear evidence of effectiveness of NEO-HT compared to chemotherapy (CT) reserve its use for patients with old age or frail conditions. However, the low pathologic complete response rate (pCR) obtained with tamoxifen or aromatase inhibitors (AIs) alone does not make NEO-HT as a suitable option for the neoadjuvant treatment of HR+ HER2-. The use of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors palbociclib, ribociclib and abemaciclib of the mammalian target of rapamycin (mTOR) inhibitor everolimus and of the phosphoinositide 3 kinase (PI3K) inhibitor taselisib together with endocrine therapy (ET) has become a standard in advanced breast cancer, showing clinical effectiveness and significantly prolonging median progression-free survival compared to ET only. In the early phase disease, the use of ET together with CDK 4/6, mTOR and PI3K inhibitors is still investigational. Data from recent studies are promising even though less impressive than in metastatic setting. In this context, the use of genomic-transcriptomic tools (such as ONCOTYPE, PAM50) and the identification of novel biomarkers (ESR1, PI3Kca, PDGF-R) on tissue or with liquid biopsy could help to select patient prone to respond to endocrine-combined therapy and able to achieve pCR. With our review, we aimed at evaluating the current state of the art in the treatment of locally advanced breast cancer with NEO-HT.

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“…Palbociclib was tested in combination with letrozole 2.5 mg/day in the PALOMA-1 and PALOMA-2 trial, for AIsensitive patients, [6][7][8]37] and in combination with fulvestrant 500 mg every 28 days in the PALOMA-3 trial, for AI-resistant [11,[38][39][40]. Ribociclib was investigated in combination with letrozole 2.5 mg/day in the MONALEESA-2 trial for AI-sensitive post-menopausal women [12,15,16,[41][42][43][44], in combination with tamoxifene or NSAI (with goserelin to suppress ovarian function) in premenopausal AI-sensitive women in the MONALEESA-7 trial [16,45], and in combination with fulvestrant both for AI-sensitive and AIresistant patients in the MONALEESA-3 trial [17]. Finally, abemaciclib was used in combination with anastrozole 1 mg/day or letrozole 2.5 mg/day, as per physician choice, for AI-sensitive patients in the MONARCH-3 trial, [19,20] and in combination with fulvestrant 500 mg every 28 days for AI-resistant patients in the MONARCH-2 trial [18,24].…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Progression free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: a systematic review and meta-analysis

Piezzo

Chiodini

Riemma

et al. 2020

Preprint

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PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

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Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial

Cited by 93 publications

References 25 publications

Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of CDK4/6 inhibitors on the current treatment paradigm

Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of CDK4/6 inhibitors on the current treatment paradigm

<p>Strategies for Increasing the Effectiveness of Aromatase Inhibitors in Locally Advanced Breast Cancer: An Evidence-Based Review on Current Options</p>

Progression free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: a systematic review and meta-analysis

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