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Palbociclib and breast

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https://www.readbyqxmd.com/read/29470723/cyclin-dependent-kinase-4-6-inhibitors-as-first-line-treatment-for-post-menopausal-metastatic-hormone-receptor-positive-breast-cancer-patients-a-systematic-review-and-meta-analysis-of-phase-iii-randomized-clinical-trials
#1
Allan Ramos-Esquivel, Hellen Hernández-Steller, Marie-France Savard, Denis Ulises Landaverde
BACKGROUND: To compare the efficacy and toxicity of the combination of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors and nonsteroidal aromatase inhibitors (AI) versus AI alone as first-line therapy for patients with advanced hormone receptor-positive breast cancer. MATERIALS AND METHODS: Phase III randomized clinical trials (RCT) were identified after a systematic review of electronic databases. A random-effect model was used to determine the pooled hazard ratio (HR) for progression-free survival (PFS) using the inverse-variance method...
February 22, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29452249/expression-and-therapeutic-implications-of-cyclin-dependent-kinase-4-cdk4-in-osteosarcoma
#2
Yubing Zhou, Jacson K Shen, Zujiang Yu, Francis J Hornicek, Quancheng Kan, Zhenfeng Duan
Overexpression and/or hyperactivation of cyclin-dependent kinase 4 (CDK4) has been found in many types of human cancers, and a CDK4 specific inhibitor, palbociclib, has been recently approved by the FDA for the treatment of breast cancer. However, the expression and the therapeutic potential of CDK4 in osteosarcoma remain unclear. In the present study, CDK4 was found to be highly expressed in human osteosarcoma tissues and cell lines as compared with normal human osteoblasts. Elevated CDK4 expression correlated with metastasis potential and poor prognosis in osteosarcoma patients as determined by immunohistochemical analysis in a human osteosarcoma tissue microarray (TMA)...
February 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29436583/antiproliferative-effects-of-the-cdk6-inhibitor-pd0332991-and-its-effect-on-signaling-networks-in-gastric-cancer-cells
#3
Daguang Wang, Yabin Sun, Wei Li, Fei Ye, Yang Zhang, Yuchen Guo, David Y Zhang, Jian Suo
PD0332991 (palbociclib/Ibrance®) is a cyclin-dependent kinase (CDK)4/6 inhibitor that has recently been approved for the treatment of estrogen receptor‑positive advanced breast cancer. The present study investigated the antiproliferative effects of PD0332991 on gastric cancer (GC) cells and the underlying molecular mechanisms. The activity of PD0332991 was tested in several GC cell lines, including AGS, KATO‑Ⅲ, NCI‑N87 and HS746T. Growth inhibitory activity of PD0332991, alone or in combination with fluorouracil (5‑FU), was measured by MTT assay...
February 6, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29399694/mechanisms-of-the-cdk4-6-inhibitor-palbociclib-pd-0332991-and-its-future-application-in-cancer-treatment-review
#4
Minghui Liu, Hongyu Liu, Jun Chen
An uncontrolled cell cycle is an obvious marker of tumor cells. The G1‑S phase is an important restriction point in the normal cell cycle, but in cancer cells the restriction function is reduced, leading to uncontrolled cell proliferation. Two cyclin‑dependent kinases (CDKs), CDK4 and CDK6, play a crucial role in the G1‑S phase transition. Inhibitors of CDK4/6 are presently the subjects of numerous studies, and PD 0332991, an inhibitor of CDK4/6, has been used to treat hormone receptor (HR)‑positive, advanced‑stage breast cancer...
January 19, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29398467/complete-response-to-single-agent-palbociclib-in-metastatic-breast-cancer-a-case-report
#5
Sri Lakshmi Hyndavi Yeruva, Mehrbod Som Javadi, Vered Stearns
No abstract text is available yet for this article.
December 21, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29374415/-inhibitors-of-cyclin-dependent-kinases-cdk-a-new-group-of-medicines-in-therapy-of-advanced-breast-cancer
#6
EDITORIAL
Tomasz Sarosiek
Cyclin-dependent kinases (CDKs) are a family of enzyme proteins present in cell nuclei that regulate the various stages of the cell cycle. They act as proto-oncogens, and increased expression of some of these proteins (CDK4 and CDK6) is observed in breast cancer cells and associated with decreased sensitivity to anti-estrogen therapy. CDK inhibitors are chemicals that inhibit the enzymatic activity of specific CDKs. Currently three drugs in this group are available on the market and are registered for the treatment of advanced HR-positive, HER2-negative breast cancer...
January 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29360932/impact-of-palbociclib-plus-letrozole-on-patient-reported-health-related-quality-of-life-results-from-the-paloma-2-trial
#7
H S Rugo, V Diéras, K A Gelmon, R S Finn, D J Slamon, M Martin, P Neven, Y Shparyk, A Mori, D R Lu, H Bhattacharyya, C Huang Bartlett, S Iyer, S Johnston, J Ettl, N Harbeck
Background: Patient-reported outcomes are integral in benefit-risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (HRQOL) for patients with metastatic breast cancer receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone). Patients and Methods: Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer were randomized 2:1 to palbociclib plus letrozole (n=444) or placebo plus letrozole (n=222)...
January 19, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29360661/palbociclib-has-no-clinically-relevant-effect-on-the-qtc-interval-in-patients-with-advanced-breast-cancer
#8
Chandrasekar Durairaj, Ana Ruiz-Garcia, Eric R Gauthier, Xin Huang, Dongrui R Lu, Justin T Hoffman, Richard S Finn, Anil A Joy, Johannes Ettl, Hope S Rugo, Jenny Zheng, Keith D Wilner, Diane D Wang
The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14...
January 22, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#9
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29344106/overall-survival-and-progression-free-survival-with-endocrine-therapy-for-hormone-receptor-positive-her2-negative-advanced-breast-cancer-review
#10
REVIEW
Tomás Reinert, Carlos H Barrios
We reviewed randomized phase II/III trials comparing first- or second-line endocrine therapy as monotherapy or in combination with targeted therapies for treatment of postmenopausal patients with hormone receptor-positive advanced breast cancer. First-line was defined as treatment for endocrine therapy-naïve advanced breast cancer or advanced disease treated with endocrine therapy in the adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for advanced breast cancer following disease progression on endocrine therapy for advanced disease...
November 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29342248/clinical-considerations-of-the-role-of-palbociclib-in-the-management-of-advanced-breast-cancer-patients-with-and-without-visceral-metastases
#11
N C Turner, R S Finn, M Martin, S-A Im, A DeMichele, J Ettl, V Diéras, S Moulder, O Lipatov, M Colleoni, M Cristofanilli, D R Lu, A Mori, C Giorgetti, S Iyer, C Huang Bartlett, K A Gelmon
Background: This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods: Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N=521) and postmenopausal women untreated for ABC (PALOMA-2; N=666) were randomized 2:1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo...
January 11, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29338448/the-safety-of-palbociclib-for-the-treatment-of-advanced-breast-cancer
#12
Tom Degenhardt, Rachel Wuerstlein, Tanja Eggersmann, Nadia Harbeck
Despite improvements in the diagnosis and management of early stage breast cancer, about one third of the patients still progress to metastatic disease. Most of the patients with metastatic breast cancer have a hormone receptor positive and human epidermal growth factor receptor 2 negative subtype with a median survival of more than 3 years. For these patients, endocrine therapy with its favorable toxicity profile is the current standard of care. However, patients with metastatic breast cancer have an incurable disease...
January 17, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29337187/metabolomics-reveals-that-dietary-xenoestrogens-alter-cellular-metabolism-induced-by-palbociclib-letrozole-combination-cancer-therapy
#13
Benedikt Warth, Philipp Raffeiner, Ana Granados, Tao Huan, Mingliang Fang, Erica M Forsberg, H Paul Benton, Laura Goetz, Caroline H Johnson, Gary Siuzdak
Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications...
January 10, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29335521/non-canonical-roles-of-pfkfb3-in-regulation-of-cell-cycle-through-binding-to-cdk4
#14
Wenzhi Jia, Xiaoping Zhao, Li Zhao, Hui Yan, Jiajin Li, Hao Yang, Gang Huang, Jianjun Liu
There is growing interest in studying the molecular mechanisms of crosstalk between cancer metabolism and the cell cycle. 6-phosphate fructose-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a well-known glycolytic activator that plays an important role in tumorigenesis. We investigated whether PFKFB3 was directly involved in oncogenic signaling networks. Mass Spectrometry showed that PFKFB3 interacts with cyclin-dependent kinase (CDK) 4, which controls the transition from G1 phase to S phase of the cell cycle...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29330290/dual-inhibition-of-cdk4-and-cdk2-via-targeting-p27-tyrosine-phosphorylation-induces-a-potent-and-durable-response-in-breast-cancer-cells
#15
Priyank Patel, Vladislav Tsiperson, Susan R S Gottesman, Jonathan Somma, Stacy W Blain
Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib, have shown clinical efficacy, but primary or secondary resistance has emerged as a problem. To develop more effective therapeutic approaches, investigation is needed into the mechanisms of resistance or adaption. Here, it is demonstrated that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested breast cancer cells, suggesting that inhibition of both kinases is required to achieve durable response. In addition, a novel strategy is described to inhibit tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2 and CDK4...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29326029/neoadjuvant-treatment-with-trastuzumab-and-pertuzumab-plus-palbociclib-and-fulvestrant-in-her2-positive-er-positive-breast-cancer-na-pher2-an-exploratory-open-label-phase-2-study
#16
Luca Gianni, Giancarlo Bisagni, Marco Colleoni, Lucia Del Mastro, Claudio Zamagni, Mauro Mansutti, Milvia Zambetti, Antonio Frassoldati, Raffaella De Fato, Pinuccia Valagussa, Giuseppe Viale
BACKGROUND: In the neoadjuvant setting, blockade of HER2 plus use of an aromatase inhibitor in patients with HER2-positive and oestrogen receptor (ER)-positive breast cancer leads to a pathological complete response in 21% of patients. Convergence of HER2 and ER signals on RB1 suggests that a combined pharmacological intervention directed to these targets could be synergistic. To test this approach, we combined palbociclib to block RB1, fulvestrant to block ER, and trastuzumab with pertuzumab to block HER2 in patients with HER2-positive, ER-positive breast cancer...
January 8, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29306306/use-of-oral-antineoplastic-in-special-situations-in-a-third-level-hospital-real-life-results
#17
Carmen Garcia-Muñoz, Pedro Pablo Rodriguez-Quesada, José Miguel Ferrari-Piquero
OBJECTIVE: To analyse the effectiveness and safety of oral antineoplastic drugs  (ANEOs) that are authorized in special situations in a third-level hospital and to  compare the results obtained with the clinical evidence used for this  authorization. METHOD: Descriptive observational and retrospective study. We included all  adult patients who started treatment with ANEO in special situations during the  year 2016. We collected demographic, treatment-related and clinical variables  (overall survival (OS), progression-free survival (PFS))...
January 1, 2018: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/29261702/combination-of-palbociclib-with-enzalutamide-shows-in-vitro-activity-in-rb-proficient-and-androgen-receptor-positive-triple-negative-breast-cancer-cells
#18
Chun-Yu Liu, Ka-Yi Lau, Chia-Chi Hsu, Ji-Lin Chen, Chia-Han Lee, Tzu-Ting Huang, Yi-Ting Chen, Chun-Teng Huang, Po-Han Lin, Ling-Ming Tseng
OBJECTIVES: Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models...
2017: PloS One
https://www.readbyqxmd.com/read/29247442/efficacy-of-palbociclib-plus-fulvestrant-after-everolimus-in-hormone-receptor-positive-metastatic-breast-cancer
#19
Pauline du Rusquec, Clément Palpacuer, Loic Campion, Anne Patsouris, Paule Augereau, Carole Gourmelon, Marie Robert, Laurence Dumas, Folliard Caroline, Mario Campone, Jean-Sébastien Frenel
BACKGROUND: Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population. METHODS: From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed...
December 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29236940/polyclonal-rb1-mutations-and-acquired-resistance-to-cdk-4-6-inhibitors-in-patients-with-metastatic-breast-cancer
#20
R Condorelli, L Spring, J O'Shaughnessy, L Lacroix, C Bailleux, V Scott, J Dubois, R J Nagy, R B Lanman, A J Iafrate, F Andre, A Bardia
Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre and post genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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