Risk of hypocalcemia in cancer patients treated with cabozantinib: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17067-e17067
Author(s):  
Adam Khorasanchi ◽  
Shenhong Wu
Keyword(s):  
Cancer Patients ◽  
Fixed Effects ◽  
Calcium Metabolism ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
High Grade ◽  
Fixed Effects Model ◽  
Increased Risk ◽  
Grade 3 ◽  
Tumor Types

e17067 Background: Cabozantinib as a multiple tyrosine kinase inhibitor has been used extensively in cancer treatment and clinical trials, and is associated with the development of hypocalcemia. Its impact on calcium metabolism is not clear. We have performed a meta-analysis to determine the overall risk of hypocalcemia with cabozantinib in cancer patients. Methods: Databases including PubMed and Google Scholar until January 2020 were used to identify relevant studies. Studies of patients assigned to cabozantinib with available data on hypocalcemia were included. Incidence and relative risk (RR) of hypocalcemia were calculated using a random-effects or fixed effects model, depending on the heterogeneity of the included studies. Results: 88 articles were screened with a total of eight studies including 1,460 cancer patients were selected for analysis. For patients receiving cabozantinib, the overall incidences of all-grade and high-grade (grade 3 or 4) hypocalcemia were 15.5% (95% CI: 12.1-42.5%) and 3.5% (95% CI: 1.1-6.8%), respectively. The incidences of all-grade and high-grade hypocalcemia varied significantly with tumor types and cabozantinib dose. Cabozantinib was associated with a significantly increased risk of all-grade and high-grade hypocalcemia with RR of 6.2 (95% CI: 2.6-14.5, p < 0.001) and 10.7 (95% CI: 2.0-56.2, p = 0.005) in comparison with controls including placebo or sunitinib. Conclusions: Cabozantinib was associated with a significantly increased risk of developing all-grade and high-grade hypocalcemia in cancer patients. Further studies are needed to understand the effect of cabozantinib on calcium metabolism and patient outcome.

scholarly journals Incidence and Risk of Hypertension in Cancer Patients Treated With Atezolizumab and Bevacizumab: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Linhan Jiang ◽  
Xiaoxia Tan ◽  
Jun Li ◽  
Yaling Li
Keyword(s):  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cardiovascular Complications ◽  
High Grade ◽  
Fixed Effects Model ◽  
Total Risk ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

PurposeThis study aims to inform previous clinical assessments to better understand the total risk of hypertension with atezolizumab and bevacizumab (hereafter referred to as “A-B”) in cancer patients, and reduce future incidence of hypertension-related cardiovascular complications.MethodsDatabases, including PubMed, Embase, Cochrane, and Web of Science were searched to identify relevant studies, which were retrieved from inception to March 6, 2021. Studies focused on cancer patients treated with A-B that provided data on hypertension were included. Statistical analyses were conducted to calculate hypertension incidence and relative risk (RR) with a random-effects or fixed-effects model, hinging on heterogeneity status.ResultsTen studies including 2106 patients with renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), ovarian cancer, anal cancer, neuroendocrine tumors (NETs), and cervical cancer were selected for this meta-analysis. For patients treated with A-B, the all-grade and high-grade (grade 3) hypertension incidence were 31.1% (95% CI: 25.5-37.3) and 14.1% (95% CI: 10.9-18.1), respectively. No significant difference was observed in all-grade hypertension incidence between RCC and a non-RCC patients (32.9% [95% CI: 25.3-42.6] v.s. 29.2% [95% CI: 19.7-39.6)]). However, the number of high-grade hypertension incidence in RCC patients (9.4% [95% CI: 4.1-21.3]) was lower than that of non-RCC patients (15.6% [95% CI: 12.8-19.1]). RCC or HCC patients who received the A-B treatment were associated with significantly increased risk of all-grade hypertension with a RR of 7.22 (95% CI: 3.3-15.7; p = 0.6) compared with patients treated with atezolizumab.ConclusionsCancer Patients treated with atezolizumab and bevacizumab have a significantly increased risk of hypertension. Sufficient monitoring is highly recommended to prevent the consequences of treatment-induced hypertension and other cardiovascular complications.

Risk of hyperglycemia attributable to everolimus in renal cell and non–renal cell carcinoma patients: A meta-analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 515-515
Author(s):  
Kevin Y Xu ◽  
Raji Shameem ◽  
Shenhong Wu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Renal Cell ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Phase Iii ◽  
Close Monitoring ◽  
High Grade ◽  
Tumor Types

515 Background: Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, everolimus’ specific impact on hyperglycemia has not been well understood. We performed a meta-analysis to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Methods: PubMed and ASCO conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without additional cancer therapies. Heterogeneity tests were performed to examine between-study differences in hyperglycemia. The incidence and relative risk of all-grade and high-grade hyperglycemia attributable to everolimus were determined using random- or fixed-effects models. Results: A total of 7 phase III and 2 phase II RCTs with various tumors were included in our analysis. Everolimus significantly increased the risk of all-grade (RR = 2.60, 95% CI: 2.03-3.31, P < 0.001) and high-grade (RR = 3.00, 95% CI: 1.72-5.23; P < 0.001) hyperglycemia. The incidences of all-grade and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI: 3.4-13.2%) and 2.5% (95%: 1.2-4.9%) respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (P < 0.001), with the highest incidence seen in renal cell carcinoma (27.2%, 95% CI: 22.2-32.8%) and the lowest in breast cancer (3.3%, 95% CI: 1.3-8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusions: The specific contribution of everolimus to both all-grade and high-grade hyperglycemia may be modified significantly by tumor types. Close monitoring should be given to patients with renal cell carcinoma.

Risk of skin rash with the proteasome inhibitor bortezomib: Updated systematic review and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9092-9092
Author(s):  
Emily Christine Case ◽  
Shenhong Wu ◽  
John F. Gerecitano ◽  
Mario E. Lacouture
Keyword(s):  
Skin Rash ◽  
Proteasome Inhibitor ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Significant Risk ◽  
Phase Iii ◽  
High Grade ◽  
Fixed Effects Model ◽  
Increased Risk ◽  
American Society

9092 Background: Rash is a common, adverse event to the novel proteasome inhibitor bortezomib (Velcade). Indicated for the treatment of multiple myeloma and mantle cell lymphoma, bortezomib is the first proteasome inhibitor approved by regulatory agencies. Because the incidence of bortezomib-induced skin rash varies widely in published manuscripts, we performed a systematic literature review and meta-analysis to determine the incidence and overall risk. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology and The American Society of Hematology annual meetings (1998 to July 2011) to identify relevant clinical studies. Eligible studies included prospective clinical phase II and phase III trials, with data on the incidence of rash in patients taking 1.3mg/m2, 1.5mg/m2, or 1.6 mg/m2 of bortezomib intravenously either weekly or twice weekly. The incidence of rash and relative risk (RR) were calculated using random-effects or fixed-effects model, depending on the heterogeneity of included studies. Results: A total of 2,616 patients with various hematologic and solid malignancies from 35 clinical trials were included for analysis. Among patients receiving twice weekly bortezomib, the summary incidence of all-grade and high-grade rash were 18.8 % (95% CI: 14.9% to 23.5%) and 3.6 % (95% CI: 2.3% to 5.7%), respectively. We found no significant increase in all grade rash incidence with higher doses of bortezomib: 19.3 % (95% CI: 15% to 24.5%) and 20.8% (95% CI: 11.6% to 34.4%) for doses of 1.3 mg/m2 and 1.5 mg/m2, respectively. In addition, bortezomib was associated with an increased risk in both all grade (RR: 19.70, 95% CI: 8.73 to 44.44, p<0.001) and high-grade rash (RR: 5.35, 95% CI: 2.16 to 13.29, p<0.001), compared to controls. Weekly bortezomib is associated with lower risk of rash compared to twice weekly dosing (incidence 3.9% versus 18.8%, p=0.001). Conclusions: Bortezomib is associated with a significant risk of developing rash with a higher risk among patients receiving twice weekly dosage. Management of rash to bortezomib is critical to prevent a negative effect on quality of life and dose modifications, both of which affect clinical outcome.

Incidence and risk of neutropenia with palbociclib in patients with cancer: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12530-e12530
Author(s):  
Yan Mao ◽  
Janice Lu ◽  
Haibo Wang ◽  
Gang Nie
Keyword(s):  
Systematic Review ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Significant Risk ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
High Grade ◽  
Fixed Effects Model ◽  
Patients With Cancer ◽  
Increased Risk

e12530 Background: Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 and has improved the progression-free survival of estrogen receptor positive, metastatic breast cancer (MBC). Its application in other cancers is also undergoing clinical evaluation. Neutropenia, especially high grade (grade 3 or 4), is one of the major side-effects of palbociclib, and the incidence was reported too vary in different studies. In order to better understand the overall risk of palbociclib associated neutropenia, we conducted a systematic review and meta-analysis. Methods: We conducted a systematic literature search (including Medline, Web of Science to November, 2016 and abstracts presented at the ASCO annual meetings from 2009 to 2016). Eligible studies include prospective clinical trials of patients with cancer treated with palbociclib on a 125mg daily 3/4 week schedule and have available data on neutropenia. The incidence and relative risk (RR) of neutropenia were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. Results: Eight studies published between 2012 and 2016 included a total of 1515 patients with cancer were eligible for analysis. For patients treated with palbociclib, the overall incidence of all-grade and high grade neutropenia were 77.4% (95% CI 70.9-82.8%) and 60.9% (57.8–63.8%), respectively. Surprisingly, the incidence of neutropenia was significantly different between MBC patients and non-MBC patients (all grade: RR 1.26 [95% CI 1.01–1.56], p = 0.041; high-grade: RR 1.57 [1.23–2.00], p = 0.000) who received palbociclib. Palbociclib was associated with a significantly increased risk of all-grade neutropenia in patients with cancer with an RR of 15.03 (10.17–22.21, p < 0.001) compared with controls. Conclusions: Patients with cancer who received palbociclib have a significant risk of developing neutropenia, especially MBC patients. It is strongly recommended to monitor these patients who are treated with palbociclib to adjust dose, treatment intervals, and avoid infections.

Risk of rash associated with lenalidomide in multiple myeloma and myelodisplastic syndrome: A systematic review of the literature and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18571-e18571
Author(s):  
Benjamin C Garden ◽  
Beatrice Nardone ◽  
Shenhong Wu ◽  
Dennis P. West ◽  
Romala Emmanuel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Significant Risk ◽  
High Grade ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

e18571 Background: Indications of lenalidomide (Len) include treatment of multiple myeloma (MM) in combination with dexamethasone (Dex) and myelodyplastic syndrome (MDS). The reported incidence and risk of rash varies widely and has been inconsistently reported in trials. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from PubMed (1998-2011), abstracts presented at ASCO conferences (2004-2011) and the Web of Science database (1998-2011). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received daily Len doses of either 10mg or 25 mg with or without 40mg of Dex. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 1,127 patients in 15 trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 29.9% (95% CI: 24.8- 35.5) and 3.8% (95% CI: 2.7-5.5), respectively. Len was associated with increased risk of all-grade rash (RR=1.7, 95% CI: 1.3-2.3; P<0.001) when compared to patients treated with a placebo and Dex. Risk of high-grade rash was increased (RR=3.7, 95% CI: 0.8-16.0) with a trend toward statistical significance (P=0.08). No significant difference in incidence of all-grade rash between patients receiving LEN doses of 10mg or 25mg (25.6%, 95% CI: 19.6-32.8% vs. 30.8%, 95% CI: 24.7-37.7%, respectively, p=0.28) was observed. Similarly, no difference was observed between patients receiving LEN monotherapy or in combination with Dex (31.0%, 95% CI: 26.6-43.3% and 23.8%, 95% CI: 14.9-35.8%, respectively, p=0.17). Conclusions: Patients with MM or MDS who are treated with Len are at significant risk for developing rash. The risk appears to be independent of LEN dosage or in combination with Dex. Further studies for prevention and treatment of this untoward toxicity are needed in order to maintain patient’s quality of life and minimize the need for dose modification, all of which may impact clinical outcome.

Tolerability of dual checkpoint blockade with nivolumab and ipilimumab: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15149-e15149
Author(s):  
Alejandro Ramon Carvajal ◽  
Judy Huang ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Risk Mitigation ◽  
Meta Analysis ◽  
Checkpoint Blockade ◽  
Discontinuation Rate ◽  
Fixed Effects Model ◽  
Increased Risk

e15149 Background: The dual checkpoint blockade of PD-1 and CTLA-4 with nivolumab and ipilimumab have been used extensively for cancer immunotherapy in clinical practice and trials due to its efficacy. A critical concern is the tolerability of the combination due to the increased risk of severe immune-mediated adverse events. A meta-analysis of clinical trials was performed to assess the treatment tolerability measured as discontinuation due to adverse events. Methods: A search through PubMed as well as abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until December 2019 was performed to identify clinical trials in which the combination of nivolumab and ipilimumab was given to cancer patients. Eligible clinical trials reported a discontinuation rate due to adverse events for the groups of patients receiving nivolumab and ipilimumab. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals. Results: Seven clinical studies which included a total of 3,213 patients (combo: 1746, control: 1467) with various cancers were selected. Overall, the intolerability of nivolumab and ipilimumab measured as the summary incidence of discontinuation due to adverse events was 25.1% (95% CI: 17.8-34.1%). The rate varied significantly with the type of cancer (P < 0.001). The lowest discontinuation rate was in uveal melanoma, with a rate of 11% (95% CI: 2.9-34.2%), and the highest discontinuation rate was in melanoma at 46.3% (95% CI: 36.6-56.4%). In comparison with chemotherapy controls from randomized controls, the intolerability was significantly higher with an relative risk of 2.1 (95% CI: 1.78-2.84) for the combination. Conclusions: There is a substantial risk for intolerability in cancer patients receiving the combination nivolumab and ipilimumab. Further studies are needed for risk mitigation.

scholarly journals Association between early bronchiolitis and the development of childhood asthma: a meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043956
Author(s):  
Guizuo Wang ◽  
Dong Han ◽  
Zhengdong Jiang ◽  
Manxiang Li ◽  
Shumei Yang ◽  
...  
Keyword(s):  
Early Life ◽  
Fixed Effects ◽  
Late Onset ◽  
Meta Analysis ◽  
Later Life ◽  
Analysis Data ◽  
Fixed Effects Model ◽  
Case Control Studies ◽  
Increased Risk ◽  
Registration Number

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant.ConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

scholarly journals Increased Risk of High-Grade Hypertension With Bevacizumab in Cancer Patients: A Meta-Analysis

2010 ◽  
Vol 23 (5) ◽  
pp. 460-468 ◽  
Author(s):  
V. Ranpura ◽  
B. Pulipati ◽  
D. Chu ◽  
X. Zhu ◽  
S. Wu
Keyword(s):  
Cancer Patients ◽  
Meta Analysis ◽  
High Grade ◽  
Increased Risk

scholarly journals Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trials ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

scholarly journals Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies

2017 ◽  
Vol 17 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Kejia Hu ◽  
David Frederick Callen ◽  
Jiayuan Li ◽  
Hong Zheng
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Overall Survival ◽  
Cancer Patients ◽  
Dose Response ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Breast Cancer Patients ◽  
Fixed Effects Model ◽  
Vitamin D Levels

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.

Sign in / Sign up

Export Citation Format

Share Document