Increased Risk of Serious Hemorrhage with Bevacizumab in Cancer Patients: A Meta-Analysis

Hapani, Sanjaykumar; Sher, Amna Falak; Chu, David; Wu, Shenhong

doi:10.1159/000314980

Cited by 156 publications

(96 citation statements)

References 81 publications

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“…Indeed, several recent meta-analyses have shown that the use of bevacizumab significantly increases the risk of developing anti-VEGF adverse events, including hypertension [5], congestive heart failure (CHF) [6], arterial thrombosis [7], hemorrhage [8,9], proteinuria [10,11] and gastrointestinal perforation [12,13]. Additionally, high-grade infection (Grades 3-4) is a rare but potentially life-threatening adverse event with bevacizumab; this has been observed in clinical trials with an incidence ranging from 0% to 23.2% [14,15].…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab increases the risk of infections in cancer patients: A systematic review and pooled analysis of 41 randomized controlled trials

Zhang

et al. 2015

Critical Reviews in Oncology/Hematology

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Section: Introductionmentioning

confidence: 99%

Bevacizumab increases the risk of infections in cancer patients: A systematic review and pooled analysis of 41 randomized controlled trials

Zhang

et al. 2015

Critical Reviews in Oncology/Hematology

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“…The safety profile of bevacizumab documented in the NO16966 trial showed that the concomitant anticoagulation therapy did not increase the risk of bleeding [7]. In a meta-analysis from 20 randomized trials, bevacizumab significantly increased the risk of serious haemorrhage with a relative risk of 1.91 (95% CI 1.36-2.68) [16]. Therefore, cautious monitoring of bleeding is important for all the patients receiving bevacizumab.…”

Section: Discussionmentioning

confidence: 99%

An Open-Label Safety Study of First-Line Bevacizumab in Combination with Standard Chemotherapy in Chinese Patients with Metastatic Colorectal Cancer Treated in an Expanded Access Program in Taiwan

et al. 2013

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Objective: An increased risk of serious adverse effects related to bevacizumab has been observed in many Western studies for metastatic colorectal cancer. To evaluate the safety of bevacizumab in Chinese patients, a safety study was conducted in Taiwan. Methods: Bevacizumab was provided by the Expanded Access Program in combination with first-line chemotherapy per investigator's choice. The primary objective is the safety profile, particularly the targeted adverse events such as proteinuria, bowel perforation, hypertension, wound healing complication, thromboembolism and bleeding. The second objectives include time to disease progression and overall survival time. Patients with major surgical procedure performed within the 28 days of bevacizumab were excluded from this study. Results: Forty patients were eligible for intent-to-treat analysis. The overall rate of objective response and disease control was 55.2 and 81.6%. The median time to disease progression and overall survival were 11.9 and 22.9 months. The actuarial 2-year survival was 46.6%. Regarding toxicity, 7 subjects (17.5%) had serious adverse effects related to study treatment. None of the patients in this cohort had arterial thrombotic events and bowel perforation. Conclusions: Bevacizumab demonstrates a similar activity and safety profile in Chinese patients. Life-threatening bowel complications were avoided in this study by excluding patients with major surgery within the first 28 days.

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“…Adding bevacizumab to standard chemotherapy entails the occurrence of further side effects (typical of a treatment with bevacizumab), with a worsening of the comprehensive expected safety profile of the treatment. As reported by two recent systematic reviews of literature [27,28], hypertension, proteinuria, bleeding or thrombotic events can be expected in patients treated with a bevacizumab-containing regimen, and these side effects can play a negative role in patients with advanced NSCLC and an often compromised performance status. Indeed, the number of treatment-related deaths is quite high in both the E4599 and AVAiL trials, with an unfavorable profile for all the bevacizumab-containing combinations.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab in the Treatment of Advanced, Non-Squamous Non-Small Cell Lung Cancer: An Evidence-Based Approach

et al. 2011

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Background: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial]. Methods: A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III–IV side effects were assumed as index of safety in both analyses. Results: 1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I² = 88.164%, p = 0.004) and overall survival (I² = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = –6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07–29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8–3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6–4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6–8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3–3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2–11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2–2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis. Conclusion: Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.

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Increased Risk of Serious Hemorrhage with Bevacizumab in Cancer Patients: A Meta-Analysis

Cited by 156 publications

References 81 publications

Bevacizumab increases the risk of infections in cancer patients: A systematic review and pooled analysis of 41 randomized controlled trials

Bevacizumab increases the risk of infections in cancer patients: A systematic review and pooled analysis of 41 randomized controlled trials

An Open-Label Safety Study of First-Line Bevacizumab in Combination with Standard Chemotherapy in Chinese Patients with Metastatic Colorectal Cancer Treated in an Expanded Access Program in Taiwan

Bevacizumab in the Treatment of Advanced, Non-Squamous Non-Small Cell Lung Cancer: An Evidence-Based Approach

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