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Open accessJournal ArticleDOI: 10.1080/14737140.2021.1852934

CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis.

04 Mar 2021-Expert Review of Anticancer Therapy (Informa UK Limited)-Vol. 21, Iss: 3, pp 283-298
Abstract: Introduction: CDK4/6 inhibitor approval for hormone-responsive breast tumors has significantly changed therapeutic algorithms, with three drugs currently approved.Areas covered: Here, we analyze th...

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Topics: Palbociclib (59%), Breast cancer (59%)

5 results found

Open accessJournal ArticleDOI: 10.3390/CANCERS13081758
07 Apr 2021-Cancers
Abstract: We analyzed thromboembolic events, recognized (AESIs), with cyclin-dependent kinase (CDK)4/6 inhibitors, using the Food and Drug Administration adverse event reporting system Methods: Thromboembolic events were characterized in terms of spectrum [venous and arterial thromboembolism (VTE; ATE)] and clinical features by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment Results: A total of 1722 thromboembolic events were retained Increased VTE reporting emerged for CDK4/6 inhibitors in the exploratory analyses (n = 659; ROR = 151; 95% CI = 139–163), with consistent disproportionality in the consolidated analyses (eg, deep vein thrombosis with abemaciclib: 17; 198; 122–319) Higher-than-expected ATE reporting was found for ribociclib, including myocardial infarction (41; 182; 133–248), with rapid onset (median latency 1 vs 6 months for other CDK4/6 inhibitors) Causality was highly probable or probable in 832% of cases, with a negligible proportion of pre-existing drug- and patient-related risk factors except for cardiovascular comorbidities (26%) Conclusions: Although causal association cannot be firmly inferred, oncologists should proactively monitor the occurrence of VTE with CDK4/6 inhibitors The unexpected distinctive increased ATE reporting with ribociclib deserves urgent clarification though large comparative population-based studies We support pharmacovigilance for the post-marketing characterization of AESIs, thus promoting real-time safe prescribing in oncology

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3 Citations

Open accessJournal ArticleDOI: 10.1016/J.BREAST.2021.08.017
Flora Zagouri1, Evangelos Terpos1, Oraianthi Fiste1, Michalis Liontos1  +12 moreInstitutions (1)
28 Aug 2021-The Breast
Abstract: Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

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Topics: Vaccination (55%), Cancer (54%), Breast cancer (54%) ... show more

1 Citations

Open accessJournal ArticleDOI: 10.3390/CANCERS13225643
11 Nov 2021-Cancers
Abstract: Purpose of review: Due to the findings of current studies and the approval of novel substances for the therapy of hormone-receptor-positive breast cancer patients, the established standards of endocrine treatment are changing. The purpose of this review is to give an overview of the history of endocrine treatment, to clarify its role in the present standard of care, and to discuss the possibilities of improvement. Recent findings: Tamoxifen, aromatase inhibitors, and fulvestrant are the main drugs that have been used for decades in the therapy of hormone-receptor-positive breast cancer patients. However, since a relevant number of women suffer at some point from disease recurrence or progression, several novel substances are being investigated to overcome resistance mechanisms by interfering with certain signaling pathways, such as the PI3K/AKT/mTOR or the CDK4/6 pathways. mTOR and CDK4/6 inhibitors were the first drugs approved for this purpose and many more are in development. Summary: Endocrine treatment is one of the best tolerable cancer therapies available. Continuous investigation serves to improve patients’ outcomes and modernize the current standard of care. Considering the resistance mechanisms and substances analyzed against these, endocrine treatment of hormone-receptor-positive breast cancer is on the brink of a new era.

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Topics: Breast cancer (57%), Cancer (54%), Tamoxifen (52%) ... show more

Open accessJournal ArticleDOI: 10.3390/MEDSCI9020042
05 Jun 2021-Medical Sciences
Abstract: Background: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20–47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. While hematological and gastrointestinal toxicities are frequently reported during treatment with CDK4/6 inhibitors, musculoskeletal symptoms are less commonly encountered. Methods: Herein, we present a retrospective study of 47 breast cancer patients who received CDK4/6 inhibitors along with endocrine therapy in our department between 01/01/2018 and 01/09/2020. Results: Median age at diagnosis was 58 years (29–81). Median duration of treatment was 8.76 months (SD: 7.68; 0.47–30.13 months). Median PFS was 24.33 months (95% CI; 1.71–46.96). Overall, toxicity was reported in 61.7% of the cases (29/47). Arthralgia was reported in 6.4% (3/47) of the patients. Hematological toxicity was reported in 51.1% (24/47) of the patients. Neutropenia was the main hematological toxicity observed (86.8%; 22/47) along with anemia (4.3%; 2/47), thrombocytopenia (2.1%; 1/47), and leukopenia (4.2%; 1/24). Conclusions: Though our data reflect a small sample size, we report a reduced arthralgia rate (6.4%) during treatment with CDK4/6 inhibitors compared with that reported in studies of AIs (20–47%).

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Topics: Breast cancer (51%)

Open accessJournal ArticleDOI: 10.3389/FONC.2021.693104
Mridula George1, Sadaf Qureshi1, Coral Omene1, Deborah Toppmeyer1  +1 moreInstitutions (1)
Abstract: Targeted therapies such as Cyclin Dependent Kinase 4 and 6 (CDK 4/6) inhibitors have improved the prognosis of metastatic hormone receptor (HR) positive breast cancer by combating the resistance seen with traditional endocrine therapy. The three approved agents currently in the market are palbociclib, ribociclib and abemaciclib. Besides the overall similarities associated with CDK4/6 inhibition, there are differences between the three approved agents that may explain the differences noted in unique clinical scenarios- monotherapy, patients with brain metastases or use in the adjuvant setting. This review article will explore the preclinical and pharmacological differences between the three agents and help understand the benefits seen with these agents in certain subgroups of patients with metastatic HR positive breast cancer.

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Topics: Palbociclib (63%), Breast cancer (63%), Metastatic breast cancer (59%) ... show more

79 results found

Open accessJournal ArticleDOI: 10.1371/JOURNAL.PMED.1000097
David Moher1, David Moher2, Alessandro Liberati3, Jennifer Tetzlaff1  +1 moreInstitutions (4)
21 Jul 2009-PLOS Medicine
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

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Topics: Systematic review (53%)

53,418 Citations

Open accessJournal ArticleDOI: 10.3322/CAAC.21492
Abstract: This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions There will be an estimated 181 million new cancer cases (170 million excluding nonmelanoma skin cancer) and 96 million cancer deaths (95 million excluding nonmelanoma skin cancer) in 2018 In both sexes combined, lung cancer is the most commonly diagnosed cancer (116% of the total cases) and the leading cause of cancer death (184% of the total cancer deaths), closely followed by female breast cancer (116%), prostate cancer (71%), and colorectal cancer (61%) for incidence and colorectal cancer (92%), stomach cancer (82%), and liver cancer (82%) for mortality Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality) Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts CA: A Cancer Journal for Clinicians 2018;0:1-31 © 2018 American Cancer Society

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Topics: Cancer registry (78%), Cancer (72%), Breast cancer (63%) ... show more

39,828 Citations

Open accessJournal ArticleDOI: 10.1038/NATURE11412
04 Oct 2012-Nature
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

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Topics: Breast cancer (56%), Exome (54%), Claudin-Low (54%) ... show more

8,025 Citations

Open accessJournal ArticleDOI: 10.1016/0092-8674(95)90385-2
Robert A. Weinberg1Institutions (1)
05 May 1995-Cell
Abstract: pRB, the product of the retinoblastoma tumor suppressor gene, operates in the midst of the cell cycle clock apparatus. Its main role is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery. In this role, pRB allows the clock to control the expression of banks of genes that mediate advance of the cell through a critical phase of its growth cycle. Loss of pRB function deprives the clock and thus the cell of an important mechanism for braking cell proliferation through modulation of gene expression.

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Topics: Retinoblastoma protein (70%), Cell Cycle Protein (65%), Restriction point (63%) ... show more

4,790 Citations