Palbociclib and Letrozole in Advanced Breast Cancer

Finn, Richard S.; Martı́n, Miguel; Rugo, Hope S.; Jones, Stephen E.; Im, Seock Ah; Gelmon, Karen A.; Harbeck, Nadia; Lipatov, Oleg; Walshe, Janice; Moulder, Stacy L.; Gauthier, Eric; Lu, Dongrui R.; Randolph, Sophia; Dièras, Véronique; Slamon, Dennis J.

doi:10.1056/nejmoa1607303

Cited by 2,041 publications

(2,131 citation statements)

References 12 publications

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“…89 The most commonly reported adverse events in the palbociclib and letrozole group compared with the letrozole alone group included neutropenia (79.5% vs 6.3%), fatigue (37.4% vs 27.5%) and nausea (35.1% vs 26.1%) and grade 1 and 2 alopecia (32.9% vs 15.8%).…”

Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 97%

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Gradishar¹,

Anderson

Balassanian

et al. 2017

J Natl Compr Canc Netw

379

346

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These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

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Section: First-line Endocrine Therapy For Metastatic Hormone Receptormentioning

confidence: 97%

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Gradishar¹,

Anderson

Balassanian

et al. 2017

J Natl Compr Canc Netw

379

346

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“…Palbociclib is a cyclin-dependent kinase (CDK) inhibitor of CDK4 and CDK6 that has been approved by the Food and Drug Administration (FDA) for the treatment of estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer(MBC), demonstrating an improvement in progression free survival (PFS) when added to antiestrogen therapy in two large phase 3 trials 1,2 .…”

mentioning

confidence: 99%

“…of patients treated with palbociclib, whereas anemia (24%) and thrombocytopenia (16%) are less common 1 . There is scarce literature about the clinical characteristics of anemia associated with palbociclib use or other CDK4/6 inhibitors.…”

mentioning

confidence: 99%

Macrocytosis and dysplastic anemia is associated with the cyclin-dependent kinase 4/6 inhibitor palbociclib in metastatic breast cancer

et al. 2017

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dysplastic anemia is associated with the Cyclin-Dependent Kinase 4/6 inhibitor palbociclib in metastatic breast cancer. Haematologica. 2017; 102:xxx doi:10.3324/haematol.2017.181941 Publisher's Disclaimer. Hematopoiesis is a dynamic process that relies on active proliferation and differentiation of stem cells into erythrocytes, myelocytes, and platelets; processes that rely on coordinated progression through various phases of the cell-cycle. Neutropenia is a well-recognized adverse effect of palbociclib, and rapidly reversible when the drug is interrupted, but nevertheless occurs in 80% of patients treated with palbociclib, whereas anemia (24%) and thrombocytopenia (16%) are less Figure S2). No other common causes for macrocytosis were observed, including B12/folate deficiency, liver insufficiency, or hypothyroidism (Table S1). Unilateral bone marrow aspirate/biopsy in all 3 cases revealed moderately hypocellular marrow (~ 10% cellularity) with mildly decreased myeloid/erythroid ratio, dysplastic erythroid forms including binucleated forms, nuclear budding, small hypolobated megakaryocytes, and adequate stainable iron sores ( Figure 1F-M and Figure S2). Due to pathological similarities to MDS, cytogenetic/mutational analysis was conducted that did not reveal any pathogenic chromosomal alterations or mutations (GENOPTIX's 40-gene myeloid molecular profile). Flow cytometry did not reveal an increase in leukemic blasts. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.To determine the extent of macrocytosis in a larger cohort, we evaluated hematological parameters in 34 patients who had received palbociclib for ER+ MBC between January 1, 2015and March 1, 2017 (n=34). Hematological parameters during palbociclib treatment, maximum MCV and minimum Hb, were compared to baseline values using the Wilcoxon signed-rank test.Significant change in MCV (delta MCV) was defined as Figure S4); however, when delta MCV≥10 was included as time-dependent variable, this difference was not statistically significant (HR 0.59, p=0.4).These data suggest that palbociclib use led to a macrocytic, dysplastic anemia with bone marrow changes that mimic human MDS. Therefore, CDK4 and CDK6 expression by qRT-PCR was evaluated using MDS derived (n=183) and healthy (n=17) CD34+ hematopoietic stem cells (HSCs) obtained from a large cohort of gene expression profiles. CDK6 expression was significantly lower...

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“…Recently, CDK4/6 antagonists have entered into clinical practice, with palbociclib showing potential in the treatment of breast cancer, causing either cellular quiescence or senescence (Finn et al 2016). It will be of interest to see whether such treatment will be of value in the therapy of aggressive pituitary adenomas or carcinomas.…”

Section: Molecular Targeted Treatmentmentioning

confidence: 99%

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

Angelousi¹,

Dimitriadis²,

Zografos³

et al. 2017

Endocrine-Related Cancer

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Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours, which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and in gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary, and parathyroid glands. Due to the rarity of these tumours and the lack of prospective studies, current guidelines are mostly based on retrospective data derived from surgical, locoregional and ablative therapies, and studies with systemic chemotherapy. In addition, in many of these malignancies the prognosis remains poor with individual patients responding differently to currently available treatments, necessitating the development of new personalised therapeutic strategies. Recently, major advances in the molecular understanding of endocrine tumours based on genomic, epigenomic, and transcriptome analysis have emerged, resulting in new insights into their pathogenesis and molecular pathology. This in turn has led to the use of novel MTTs in increasing numbers of patients. In this review, we aim to present currently existing and evolving data using MTT in the treatment of adrenal, pituitary and malignant parathyroid tumours, and explore the current utility and effectiveness of such therapies and their future evolution.

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Palbociclib and Letrozole in Advanced Breast Cancer

Cited by 2,041 publications

References 12 publications

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Macrocytosis and dysplastic anemia is associated with the cyclin-dependent kinase 4/6 inhibitor palbociclib in metastatic breast cancer

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

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