scholarly journals New Drugs, Old Toxicities: Pneumonitis Related to Palbociclib – A Case Report

Breast Care ◽  
2019 ◽  
Vol 15 (5) ◽  
pp. 548-552 ◽  
Author(s):  
Eudald Felip ◽  
Laia Llobera ◽  
Clara Perez-Mañá ◽  
David Quintela ◽  
Ignacio Guasch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Specific Inhibitor ◽  
Metastatic Breast ◽  
New Drugs ◽  
Cyclin Dependent Kinase ◽  
Breast Cancer Patients ◽  
Case Presentation ◽  
Cyclin Dependent Kinases ◽  
Main Adverse Effect

Background: Palbociclib is a specific inhibitor of cyclin-dependent kinases 4 and 6 that is approved for the treatment of advanced or metastatic breast cancer patients. Despite a good toxicity profile in pivotal trials, where asymptomatic neutropenia was the main adverse effect, its wider use in clinical practice may show less prevalent but serious toxicities. Case Presentation: Here, we describe a case of pneumonitis due to palbocicblib. A 57-year-old female with breast cancer with bone metastasis presented dyspnea at rest 3 months after beginning treatment with palbociclib and letrozole. Palbociclib-induced pneumonitis was considered the most probable cause after ruling out all alternatives, and the patient was successfully treated with steroids and showed complete remission. Conclusions: In summary, we present a well-documented case report of pneumonitis related to palbociclib. However, the mechanism of toxicity is still unknown, and there are as yet no reliable biomarkers to predict toxicity with cyclin-dependent kinase 4/6 inhibitors. In this case report, we alert physicians about new drugs that can provoke old toxicities.

scholarly journals Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

2017 ◽  
Vol 8 (11) ◽  
pp. 337-347 ◽  
Author(s):  
Kyrillus S. Shohdy ◽  
Shaimaa Lasheen ◽  
Loay Kassem ◽  
Omar Abdel-Rahman
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Safety Profile ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
High Grade ◽  
Cyclin Dependent Kinase ◽  
Breast Cancer Patients ◽  
Randomized Phase Ii

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12–1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09–2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07–1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19–1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29–4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25–7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87–18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44–3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

Venous thromboembolism in breast cancer patients receiving cyclin-dependent kinase inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18184-e18184
Author(s):  
Lorenzo Gervaso ◽  
Alberto J. Montero ◽  
Xuefei Jia ◽  
Alok A. Khorana
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Kinase Inhibitors ◽  
Cleveland Clinic ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Breast Cancer Patients

e18184 Background: Venous thromboembolism (VTE) complicates several anti-cancer regimens including chemotherapy and anti-angiogenic agents. Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are a new approach for hormone receptor positive (HR+) metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% for ribociclib (MONALEESA-2) to 2% for palbociclib (PALOMA-3) and 5% for abemaciclib (MONARCH-3) but these may underestimate actual rates compared to patients in clinical practice who are generally older and have greater comorbidities. Little is known about real world incidence or prevalence of VTE with CDKIs in mBC. The aim of this study was to evaluate rates of VTE in clinical practice and association with outcomes in mBC patients on CDKIs. Methods: We conducted a retrospective cohort study at Cleveland Clinic Taussig Cancer Institute, approved by the institutional review board. We identified consecutive mBC patients who received any of three FDA-approved CDKIs (palbociclib, ribociclib, abemaciclib) from 1/2015 through 12/2017. VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by electronic medical record review. Overall survival (OS), progression free survival (PFS) and time to VTE were estimated by the Kaplan-Meier method and evaluated for association with VTE using Cox proportional hazard regression. Results: The study population included 424 patients, with a median age at diagnosis of 54.76 yrs, (range 27 -85). Palbociclib was the most commonly used CDKI (n = 390, 91.8%); 27 patients (6.3%) received more than one drug. VTE during CDKI therapy occurred in 9% of patients (n = 38), including DVT in 52.6% (n = 20), PE in 18.5% (n = 7) and visceral vein thrombosis (VVT) in 15.8% (n = 6). Median time to VTE was 314 days, and 6-months rate was 4.1%. VTE was associated with numerically worse PFS and OS, but this was not statistically significant (PFS [HR 1.25, 95% CI 0.73 – 2.14, p = 0.42], OS [HR 1.60, 95% CI 0.89 – 2.87, p = 0.12]). Conclusions: VTE affected nearly 10% of breast cancer patients receiving CDKIs, 2- to 5-fold greater than reported in registration trials. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis.

Abstract 16720: Cardiovascular Toxicities of Cyclin Dependent Kinase (cdk) 4/6 Inhibitors in Metastatic Breast Cancer Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael G Fradley ◽  
Nam Nguyen ◽  
Yiqing Chen ◽  
Avirup Guha ◽  
Jenica N Upshaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Risk Mitigation ◽  
Significant Proportion ◽  
Metastatic Breast ◽  
Cancer Therapeutics ◽  
Mitigation Strategies ◽  
Cyclin Dependent Kinase ◽  
Breast Cancer Patients ◽  
Pericardial Disease

Introduction: Cyclin Dependent Kinase (CDK) 4/6 inhibitors are a novel class of cancer therapeutics which have significantly improved survival in patients with hormone receptor positive, HER2 negative metastatic breast cancer. There is little data regarding the epidemiology of cardiotoxicity with these therapies. Methods: Using the OneFlorida Data Trust , adult patients without prior cardiovascular disease who received at least one CDK 4/6 inhibitor between January 1, 2012 and December 31, 2018 were included in the analysis. CAEs identified from ICD 9/10 codes include: new hypertension (HTN); arrhythmias (excluding sudden cardiac death); new hypertension (HTN); heart failure/cardiomyopathy; ischemic heart disease, pericardial disease. Log-rank tests were performed to compare time to all-cause mortality in patients with or without CAE. Multivariable cox proportional hazard regressions were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality adjusting for age, gender, race, obesity, HTN, diabetes (DM) and hyperlipidemia (HLD). Results: A total of 1,035, predominantly female (96%) patients were included in the analysis. The mean age was 61±13 years, and CV risk factors were prevalent at baseline: obesity (17.1%), HTN (22.2%), DM (9.9%), HLD (10.5%). Cardiotoxicity occurred in 174 (16.8%) patients of which 30 (17.2%) died (p<0.001). There were 61 cases of arrhythmias with 15 (24.6%) deaths (p<0.001) and 97 cases of new HTN with 15 (15.5%) deaths (p<0.001). Unadjusted and adjusted HRs and 95% CIs for mortality are shown in the figure. Effects were similar across all CDK 4/6 inhibitors. Conclusions: Cardiotoxicity is common with CDK 4/6 inhibitors and are associated with overall increased mortality and arrhythmias and HTN accounting for a significant proportion of this finding. Patients taking CDK 4/6 inhibitors should be monitored for CAEs with aggressive risk mitigation strategies to minimize morbidity and mortality.

scholarly journals Significant up-regulation of the cyclin-dependent kinase CDK10 in primary tumors of patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cell Division ◽  
Metastatic Breast ◽  
Published Data ◽  
Cyclin Dependent Kinase ◽  
Front Line ◽  
Primary Tumors ◽  
Cyclin Dependent Kinases ◽  
Division 1 ◽  
Proliferation And Metastasis

Cancer is defined by uncontrolled cell division (1, 2). Cell division is governed by the cell cycle, a system of molecules called cyclins, which are activated by cyclin-dependent kinases, operating together to orchestrate controlled progression through G1-, S-, G2-, and M-phases (3). We report here that in human breast cancer, trastuzumab treatment is associated with significantly increased expression of the cyclin-dependent kinase CDK10. This piece of evidence, obtained through unbiased comparative transcriptome analysis of published data (4, 5), continues to illustrate a portrait of a cancer therapeutic with molecular properties associated with proliferation and metastasis, reconciling a 34% incidence of central nervous system metastases (6) in patients treated with what is considered a front-line treatment for adjuvant and metastatic breast cancer.

Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period

2004 ◽  
Vol 22 (16) ◽  
pp. 3302-3308 ◽  
Author(s):  
Fabrice Andre ◽  
Khemaies Slimane ◽  
Thomas Bachelot ◽  
Arianne Dunant ◽  
Moise Namer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Metastatic Breast ◽  
New Drugs ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Over Time

Purpose Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. Patients and Methods A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis. Results Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001). Conclusion The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.

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