Meta-analysis of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy versus endocrine therapy alone on progression-free survival (PFS) and overall survival (OS) for metastatic breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1060-1060
Author(s):  
Ranju Kunwor ◽  
Ramkaji Baniya ◽  
Maysa M. Abu-Khalaf
Keyword(s):  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Hormone Receptor Positive

1060 Background: CDK 4/6 inhibitors with Endocrine therapy (ET) are the preferred first line treatment for Hormone Receptor positive and Human Epidermal Growth factor receptor 2 negative (HR+/HER2-) MBC. Over the last few years multiple trials have shown benefit in PFS. Only two studies evaluating Ribociclib and Abemaciclib showed an OS benefit while no statistically significant OS benefit has been reported in any of the studies evaluating Palbociclib raising the possibility that this benefit may be drug specific rather than applicable to all CDK 4/6 Inhibitors. This updated meta-analysis of randomized controlled trials (RCTs) aims to assess the PFS and OS of all three CDK 4/6 inhibitors in HR+/HER2- MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science. Only the phase II and III RCTs comparing CKD 4/6 inhibitors plus ET with ET alone were eligible for this meta-analysis. The pooled analysis of Hazard Ratio (HR) was performed with Review Manager 5.3 using random effect model. Results: A total of 8 RCTs including 4338 patients with HR+/HER2- MBC were included in this meta-analysis (table). The pooled HR for PFS was 0.55 (95% confidence interval (CI), 0.50-0.59; P < .00001) and the pooled HR for OS was 0.75 (95% CI, 0.68-0.84; P < .00001). Conclusions: The result of our meta-analysis confirms the previously reported PFS benefit from CDK 4/6 inhibitors plus ET and shows an OS benefit when including RCTs of all 3 CDK 4/6 inhibitors for the treatment of HR+/HER2- MBC. [Table: see text]

scholarly journals Progression free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Michela Piezzo ◽  
Paolo Chiodini ◽  
Maria Riemma ◽  
Stefania Cocco ◽  
Roberta Caputo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Visceral Metastases ◽  
Metastatic Sites

Abstract PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

Comparative efficacy of everolimus versus fulvestrant for hormone-receptor–positive (HR+) advanced breast cancer (ABC) following progression/recurrence after first-line treatment: A network meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11602-e11602
Author(s):  
Thomas Denis Bachelot ◽  
Guy Heinrich Maria Jerusalem ◽  
Maria Cikalo ◽  
Rachael McCool ◽  
Sarah King ◽  
...  
Keyword(s):  
Endocrine Therapy ◽  
Web Sites ◽  
Meta Analysis ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Indirect Evidence ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Comparative Efficacy ◽  
Horizon Scanning

e11602 Background: Everolimus (EVE), an oral mammalian target of rapamycin (mTOR) inhibitor, is approved in combination with exemestane (EXE) to treat postmenopausal women (PMW) with HR+, human epidermal growth factor receptor-2–negative (HER2–) ABC that progressed after nonsteroidal aromatase inhibitor therapy. Fulvestrant (FUL), an estrogen receptor antagonist, is another treatment option for PMW previously treated with endocrine therapy. However, the comparative efficacy of EVE + EXE vs FUL is unknown. Methods: Six randomized, controlled trials in HR+, HER2–ABC patients were identified by systematic literature review (Cochrane library, National Horizon Scanning Centre, and NICE Web sites) that formed a network permitting indirect comparisons of EVE + EXE or EVE + tamoxifen (TAM) vs FUL: BOLERO-2, CONFIRM, EFECT, Paridaens (2008), SoFEA, and TAMRAD. All 6 trials had EXE, TAM, or FUL 250 mg as the common comparator to form the network. Relative efficacy of EVE and FUL was obtained using a Bayesian network meta-analysis based on these 6 trials. The primary endpoint was local assessment of progression-free survival (PFS) or time to progression (TTP). The hazard ratio (HR) of EVE + EXE relative to FUL and its 95% credible intervals (CrI) were calculated. Evidence of a difference between treatments is suggested by the 95% CrI not including 1. A HR <1 indicates that the hazard rate is higher in the comparator group and that the treatment is more effective. Results: EVE + EXE was found to be more efficacious for PFS/TTP than FUL 250 mg (HR = 0.47; 95% Crl, 0.38-0.58) and more efficacious than FUL 500 mg (HR = 0.59; 95% Crl, 0.45-0.77). EVE + TAM was found to be numerically better for PFS/TTP than FUL 250 mg (HR = 0.65; 95% Crl, 0.40-1.04) and numerically better than FUL 500 mg (HR = 0.81; 95% Crl, 0.49-1.33). Conclusions: The indirect evidence from this analysis suggests that EVE in combination with EXE is more efficacious than FUL 250 and 500 mg in PMW with HR+, HER2– ABC that progresses after endocrine therapy. These data should be interpreted with caution as there is no randomized trial that directly compares EVE + EXE vs FUL.

CDK 4/6 inhibitors (CDKi) + endocrine therapy (ET) in ER-positive metastatic breast cancer (mBC) patients according ET sensitivity: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12532-e12532
Author(s):  
Michela Piezzo ◽  
Maria Riemma ◽  
Daniela Cianniello ◽  
Roberta Caputo ◽  
Giuseppina Fusco ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Random Effect ◽  
Objective Response ◽  
Random Effect Model ◽  
Metastatic Breast ◽  
Pooled Analysis ◽  
P Value ◽  
Er Positive ◽  
Resistant Group ◽  
Metastatic Sites

e12532 Background: Addition of CDKi to ET in ER-positive mBC has proven effective in improving both progression-freesurvival (PFS) and Objective Response Rate (ORR). However, no randomized clinical trial (RCT) has so far shown a significant increase of Overall Survival (OS). We carried out a metanalysis of all RTCs to better characterize the efficacy of CDK4/6i in some relevant subgroups, with particular reference to OS. Methods: Literature search of main databases was carried out up to 08 Dec 2018. Hazard ratios (HRs) for PFS and OS and risk ratios (RRs) for ORR were extracted/calculated for each trial and then pooled by using both fixed and random effect model. Confidence intervals (CIs) at 95% were calculated for each statistics. Kaplan-Meier meta-curves were generated by pooling data of all trials, among ET sensitive and ET resistant pts. Results: Eight RCTs were included accounting for a total of 4580 pts, 2802 receiving a CDKi (palbociclib, ribociclib or abemaciclib) in association with ET (NSAI, tamoxifene or fulvestrant) and 1778 receiving ET alone or plus placebo. Pooled analysis of HRs showed a significant improvement in PFS, regardless ET sensitivity, disease site, number of metastatic sites and treatment free interval. Analysis of OS included 3 RCTs with a total of 1243 pts and showed a statistically significant improvement of OS (HR 0.769 [95% CI 0.638, 0.926], p-value 0.006). Pooled estimate for RR showed higher ORR in CDK 4/6 arm both in ET sensitive (RR 1.35 [95% CI 1.19, 1.52]) and ET resistant group (RR 2.19 [95% CI 1.66, 2.89]). Similarly, pts with measurable disease showed a RR of 1.34 (95% CI 1.20, 1.50) in ET sensitive group and 2.26 (95% CI 1.72, 2.96) in ET resistant group. Pooled survival curves showed an absolute benefit in PFS, both in ET sensitive (median PFS: NR vs 15 months) and ET resistant (median PFS: 19.2 vs 8.9 months). Conclusions: Our findings suggest that addition of CDKi to ET improve clinical outcome in terms of PFS, ORR and OS, irrespective of pts/tumor characteristics.

Pain medication use in patients with HR+, HER2-neg advanced breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor: A U.S. FDA pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24145-e24145
Author(s):  
Jennifer J Gao ◽  
Bellinda King-Kallimanis ◽  
Christine Hodgdon ◽  
Joyce Cheng ◽  
Mallorie Fiero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Pooled Analysis ◽  
Start Date ◽  
Hormone Receptor Positive ◽  
Pain Medications ◽  
Usage Patterns ◽  
Demographic Subgroups

e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with advanced/metastatic breast cancer (MBC). We examined PM usage patterns in pts receiving CDK 4/6 inhibitor (CDKI) based treatment. Methods: We pooled data from seven phase 3 randomized, controlled trials of CDKI + endocrine therapy in pts with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. PM were categorized as opioid (includes codeine-containing), NSAID, or other (i.e. bone-directed, antiepileptic, topical PMs). All analyzed pts received at least 1 dose of CDKI/placebo and had concomitant PM with a documented start date. Medications prescribed during hospitalizations were not included. We evaluated percent PM by demographic factors and pts with bone mets, and liver/lung mets. Results: 2416 pts met the inclusion criteria, of which 928 pts started a PM before the study and 1488 pts did not start PM before the study. Of the 1488 pts not on a PM before the study, 739 started a PM after study started, and 749 did not receive any PM at any time. Of the 739 pts who started a PM only after study start, overall, 59% were prescribed only an NSAID, 10% were prescribed only opioid, 17% were prescribed both an NSAID and opioid, and 14% were prescribed other PMs. The PM use by percent in demographic subgroups in the 1488 pts who took none or more PMs only after study start are presented in the table. Conclusions: To our knowledge, this is the first analysis of PM usage patterns in pts with MBC receiving CDKI or placebo with hormonal therapy on clinical trials. NSAID use was higher than opiates in all prespecified subgroups. Future analyses will examine the benefit of different classes of pain medications in treating symptoms of pain and whether there are differences between study treatment arms Percent PM Use by Class (Patients Who Took None or More PM Only After Study Start). [Table: see text]

scholarly journals Prognostic Value of High CXCR4 Expression in Renal Cell Carcinoma: A System Review and Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yuefeng Du ◽  
Qingzhi Long ◽  
Bing Guan ◽  
Lijun Mu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Progression Free Survival ◽  
Cxcr4 Expression ◽  
Cochrane Library

Background. Recent studies have shown that CXC chemokine receptor 4 (CXCR4) is involved in the progression and metastasis of renal cell carcinoma (RCC). However, the prognostic value of CXCR4 expression in RCC remains controversial. The aim of our meta-analysis is to evaluate the prognostic value of high CXCR4 expression in RCC.Methods. Relevant studies focused on the relationship between high CXCR4 expression and the outcome of RCC were searched in PubMed and EMBASE/Cochrane Library database. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were our evaluation index. The individual and pooled HRs with 95% confidence intervals (CIs) were analyzed.Results. A total of 1068 patients from 7 studies were included in our meta-analysis. The results suggested that high CXCR4 expression predicted a poor OS (random effect model (REM) HR = 2.77, 95% CI = 1.80−4.27) and PFS (REM HR = 4.83, 95% CI = 2.30−10.15) for RCC patients.Conclusion. The results of meta-analysis indicated that high CXCR4 expression was correlated with worse OS and PFS for patients with RCC. However, some larger samples and well-matched studies should be designed to estimate the potential prognosis of RCC patients.

scholarly journals Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Raffaella Palumbo ◽  
Rosalba Torrisi ◽  
Federico Sottotetti ◽  
Daniele Presti ◽  
Anna Rita Gambaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Receptor ◽  
Treatment Line ◽  
Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Novel oral anticoagulats for the treatment of left ventricle thrombosis: a systematic review and meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Serenelli ◽  
F Vitali ◽  
R Pavasini ◽  
E Tonet ◽  
G Pompei ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Left Ventricular ◽  
Left Ventricular Thrombus ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Ventricular Thrombus

Abstract Funding Acknowledgements Type of funding sources: None. Background novel oral anticoagulants (NOACs) are not guideline-recommanded treatment for left ventricular thrombus.  Purpose: the aim of this meta-analysis is to compare NOACs versus vitamin-K atagonsits (VKAs) efficacy in treating left ventricular thrombus (LVT). Methods: we systematically searched MEDLINE, Cochrane Library, Biomed Central, and Web of Science for trials comparing NOACs versus VKAs in the setting of LVT. Five studies, out of the 74 initially selected after first screening, were included in the meta-analysis. For the development of this meta-analysis, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. The shortlisted studies were retrieved as full articles and appraised independently by two unblinded reviewers. The Mantel-Haensel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of stroke and systemic embolism. Secondary outcome was occurrence of left ventricular thrombosis resolution during treatment.  Results: 707 patients were included in the analysis for the primary outcome. Of these, 230 were treated with NOACs and 477 with VKAs. The pooled OR for the primary outcome was 0.71 (95% CI 0.18-2.86, I2 67%), thus showing similar effect in term of ischaemic protection. A total of 698 patients, 228 on NOACs and 470 on VKAs were included in the analysis of the secondary outcome. The pooled OR for the secondary outcome pooled OR 0.97, 95% CI 0.56-1.68, I2 46%. Conclusions and Relevance: NOACs seem to have a similar efficacy profile compare to VKAs and so they should be considered as an alternative treatment for left ventricular thrombosis. Large prospective randomized clinical trials are needed to confirm this exploratory finding. Abstract Figure 1

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

scholarly journals Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Dipesh Kumar Yadav ◽  
Vishnu Prasad Adhikari ◽  
Qi Ling ◽  
Tingbo Liang
Keyword(s):  
Liver Transplant ◽  
Immunosuppressive Therapy ◽  
Meta Analysis ◽  
Severe Disease ◽  
Random Effect ◽  
Random Effect Model ◽  
Mammalian Target Of Rapamycin ◽  
Calcineurin Inhibitors ◽  
Pooled Analysis ◽  
Organ Rejection

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS.Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17–31.65; p &lt; 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85–24.22; p &lt; 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age &gt;60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities.Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

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