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

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17067 ◽

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.

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ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

Future Oncology ◽

10.2217/fon-2020-0671 ◽

2020 ◽

Author(s):

Emre Yekedüz ◽

Elif Berna Köksoy ◽

Hakan Akbulut ◽

Yüksel Ürün ◽

Güngör Utkan

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Meta Analysis ◽

Circulating Tumor Dna ◽

Random Effects Model ◽

Inverse Variance ◽

Increased Risk ◽

Significant Step ◽

Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

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Serrated Epithelial Change Is Associated With High Rates of Neoplasia in Ulcerative Colitis Patients: A Case-controlled Study and Systematic Review With Meta-analysis

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa312 ◽

2020 ◽

Author(s):

Alyssa M Parian ◽

Berkeley N Limketkai ◽

Reezwana Chowdhury ◽

Gala Godoy Brewer ◽

George Salem ◽

...

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Ulcerative Colitis ◽

Meta Analysis ◽

High Grade Dysplasia ◽

Endoscopic Surveillance ◽

Controlled Study ◽

High Grade ◽

Increased Risk ◽

Epithelial Change

Abstract Background Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC). Methods A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data. Results This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P < 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P < 0.001). Conclusion Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.

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Risk of Skin Rash in Proteasome Inhibitor Bortezomib: A Systematic Literature Review and Meta-Analysis

Blood ◽

10.1182/blood.v118.21.5120.5120 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5120-5120

Author(s):

Emily C Case ◽

Shenhong Wu ◽

John Gerecitano ◽

Mario E Lacouture

Keyword(s):

Literature Review ◽

Skin Rash ◽

Systematic Literature Review ◽

Proteasome Inhibitor ◽

Fixed Effects ◽

Meta Analysis ◽

Phase Iii ◽

High Grade ◽

Increased Risk ◽

American Society

Abstract Abstract 5120 Background: Bortezomib (VELCADE) is the first proteasome inhibitor to be approved by regulatory agencies for treatment of multiple myeloma and mantle cell lymphoma. Maculopapular rash is a common, adverse event to bortezomib. Because the summary incidence of bortezomib-induced skin rash is not well known, 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 from 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 twice weekly for two weeks followed by one week off, in a 21-day cycle. 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 2,469 patients with various hematologic and solid malignancies from 32 clinical trials were included for analysis. Among patients receiving bortezomib, the summary incidences 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 rash incidence with higher doses of bortezomib. In addition, bortezomib was associated with an increased risk in both all grade (RR:19.703, 95% CI: 8.734 to 44.446, p<0.001) and high-grade rash (RR: 5.354, 95% CI: 2.158 to 13.285, p<0.001), in comparison with controls. Conclusion: Bortezomib is associated with a significant risk of developing rash. Management of bortezomib-induced rash is critical to prevent a negative effect on quality of life and dose modifications, both of which may affect clinical outcome. Disclosures: Wu: Onyx: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Genentech: Speakers Bureau. Gerecitano:Millenium: Research Funding.

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Incidence and risk of congestive heart failure risk in renal cell cancer (RCC) and non-RCC patients treated with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.316 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 316-316 ◽

Cited By ~ 2

Author(s):

C. J. Richards ◽

Y. Je ◽

F. A. Schutz ◽

S. M. Dallabrida ◽

J. J. Moslehi ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Cancer Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Kinase Inhibitor ◽

Cell Cancer ◽

Tumor Type ◽

High Grade ◽

Increased Risk

316 Background: Sunitinib is a multitargeted receptor tyrosine kinase inhibitor that is widely used in the treatment of renal cell cancer (RCC) and several other malignancies. Congestive heart failure (CHF) has been reported with sunitinib, but the overall incidence and relative risk (RR) remain undefined. We preformed an up-to-date comprehensive meta-analysis to determine the risk of developing serious CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods: Medline databases were searched for articles from January 1966 to September 2010. Eligible studies were limited to phase II and III trials of sunitinib in cancer patients with any primary tumor type and adequate safety profile reporting. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI), using random-effects models. Results: A total of 5,497 patients were included. Overall incidence for all-grade and high-grade CHF in sunitinib-treated patients was 4.9% (95% CI, 1.6–14.1%) and 1.8% (95% CI, 0.8–3.9%), respectively. The RR of all-grade and high-grade CHF in sunitinib-treated patients compared to placebo-treated ones was 1.81 (95% CI, 1.30–2.50; p<0.0001) and 3.17 (95% CI, 1.12–8.97; p=0.030), respectively. On subgroup analysis there was no difference observed in the CHF incidence for RCC vs. non-RCC patients. No evidence of publication bias was observed. Conclusions: This is the first comprehensive report to demonstrate that sunitinib use is associated with an increased risk of significant heart failure in cancer patients. [Table: see text]

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

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.515 ◽

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.

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