Ribociclib (RIB) + fulvestrant (FUL) in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): Results from MONALEESA-3.

Slamon, Dennis J.; Neven, Patrick; Chia, Stephen; Im, Seock‐Ah; Fasching, Peter A.; DeLaurentiis, Michelino; Bianchi, Giulia; Esteva, Francisco J.; Martı́n, Miguel; Pivot, Xavier; Vidam, Gena; Wang, Yingbo; Lorenc, Cristina Karen Rodriguez; Miller, Marshall G.; Taran, Tanya; Jérusalem, Guy

doi:10.1200/jco.2018.36.15_suppl.1000

Cited by 20 publications

(16 citation statements)

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“…Grade 3 AEs reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant vs placebo plus fulvestrant) were neutropenia (47% vs 0) and leukopenia (13% vs 0), while neutropenia was the only grade 4 AE occurring in ≥ 5% of patients (7% vs 0) [25]. AE-related treatment discontinuations were rare (8% ribociclib plus fulvestrant vs 4% placebo plus fulvestrant), supporting the manageable safety profile of ribociclib-based combinations [25, 53].…”

Section: Resultsmentioning

confidence: 92%

“…A total of 726 patients were randomized 2:1 to receive ribociclib plus fulvestrant ( n = 484) or placebo plus fulvestrant ( n = 242). Patients received the study treatment either as first-line (49% ribociclib arm, 53% placebo arm; patients who had no [neo]adjuvant endocrine therapy or relapsed > 12 months after [neo]adjuvant endocrine therapy and were treatment-naïve for advanced disease) or second-line (49% ribociclib arm, 45% placebo arm; patients who had received one line of endocrine therapy for advanced disease or relapsed ≤ 12 months from completion of [neo]adjuvant endocrine therapy) treatment [25, 53]. Ribociclib plus fulvestrant significantly improved PFS vs placebo plus fulvestrant (20.5 vs 12.8 months; HR 0.59 [95% CI 0.48–0.73]; P < 0.001), and improvement was consistent for first-line (HR 0.58; 95% CI 0.42–0.80) and second-line treatment (HR 0.57; 95% CI 0.43–0.74) for advanced disease [25].…”

Section: Resultsmentioning

confidence: 99%

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Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

2018

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Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy. As most patients in this setting have already developed mechanisms of resistance to endocrine therapy, targeting biological pathways associated with endocrine resistance in combination with fulvestrant may improve outcomes. Therefore, evidence supporting a combinatorial treatment approach in the second-line setting was investigated based on a search of PubMed and ClinicalTrials.gov . Twenty-eight studies of targeted therapies plus fulvestrant as second-line treatment for HR+ ABC were identified, including three and six key randomized trials exploring cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors plus fulvestrant respectively. Additional combinations with fulvestrant included inhibitors of epidermal growth factor receptors, androgen receptor, and the bromodomain and extra-terminal family of proteins. Across the studies reviewed with available data, the addition of targeted therapies to fulvestrant resulted in clinically meaningful improvements in progression-free survival compared with fulvestrant alone. While some challenging toxicities were observed, most adverse events could be effectively managed. Selection of second-line targeted therapy for use with fulvestrant should consider prior treatment as well as the mutation status of the tumor. In conclusion, available data indicate that fulvestrant combined with agents targeting mechanisms of endocrine resistance is a promising approach. The ongoing trials identified in this review will help further inform the selection of combination treatments with fulvestrant for HR+ ABC.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

2018

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“…The phase III studies MONALEESA‐3, MONARCH‐2 and PALOMA‐3 demonstrated a median PFS of 20.5 months (first and second line combined), 16.4 months and 9.5 months in the combination arms compared with the fulvestrant monotherapy arms of 12.8, 9.3 and 4.6 months respectively, with similar HR to those seen in the first line studies . In the sub‐group of patients receiving second line ribociclib plus fulvestrant in the MONALEESA‐3 study, median PFS was 14.6 months compared to 9.1 months in the fulvestrant alone arm (HR 0.57; 95% CI, 0.43 to 0.74) …”

Section: Clinical Trial Data: Efficacymentioning

confidence: 72%

“…The efficacy data for CDK4/6 inhibitors in combination with a nonsteroidal aromatase inhibitor (NSAI) for first line treatment of HR+ HER2– metastatic breast cancer in postmenopausal women is derived from three phase III double‐blind randomized controlled trials (MONARCH‐3 6 , PALOMA‐2 15 and MONALEESA‐2 8 ) and one phase II study (PALOMA‐1 5 ) (Table ). In addition, the MONALEESA‐3 study compared ribociclib in combination with the selective estrogen receptor degrader (SERD) fulvestrant to fulvestrant plus placebo and included patients who had received one prior line of therapy as well as treatment‐naïve patients …”

Section: Clinical Trial Data: Efficacymentioning

confidence: 99%

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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“…50 Again, most patients did not experience concomitant infections, and the incidence of febrile neutropaenia was very low (1.2%). 4 Data from the MONALEESA-7 49 and MONALEESA-3 trials 52 confirmed a similar incidence of G3/G4 neutropaenia (Table S5, Supplementary material, File 1) with low rates of febrile neutropaenia (1–2%).…”

Section: Educational Modulementioning

confidence: 73%

Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication

et al. 2019

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Drug–drug interactions are of significant concern in clinical practice in oncology, particularly in patients receiving Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are typically exposed to long-term regimens. This article presents the highlights from the ‘First Workshop on Pharmacology and Management of CDK4/6 Inhibitors: Consensus about Concomitant Medications’. The article is structured into two modules. The educational module includes background information regarding drug metabolism, corrected QT (QTc) interval abnormalities, management of psychotropic drugs and a comprehensive review of selected adverse effects of palbociclib and ribociclib. The collaborative module presents the conclusions of the five working groups, each of which comprised five experts from different fields. From these conclusions positive lists of drugs for treating common comorbid conditions that can be safely administered concomitantly with palbociclib and/or ribociclib were developed.

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Ribociclib (RIB) + fulvestrant (FUL) in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): Results from MONALEESA-3.

Cited by 20 publications

References 0 publications

Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

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

Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication

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