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An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

ABSTRACT: BACKGROUND: The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue. METHODS: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab. RESULTS: Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05-1.57). This association varied significantly with tumor types (P=0.002) and chemotherapeutic agents (P=0.005) but not with bevacizumab dose (P=0.90). Increased risk was seen in patients with non-small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum. CONCLUSION: Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.

SUBMITTER: Huang H

PROVIDER: S-EPMC3943842 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

Huang Hongxin H Zheng Yayuan Y Zhu Jianhong J Zhang Jingjing J Chen Huapu H Chen Xinggui X

PloS one 20140305 3

<h4>Background</h4>The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.<h4>Methods</h4>An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio ( ...[more]

PMID: 24599121

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Project description:BackgroundThis network meta-analysis assessed the comparative risk of grade 3-5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment.MethodsPubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3-5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals.ResultsIn 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3-5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3-5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3-5 TRAEs.ConclusionsCompared with combinatorial therapy, ICI monotherapy caused lower grade 3-5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.

Project description:Background: Triple-negative breast cancer (TNBC) and HER-2 negative metastatic breast cancer (HER-2 negative MBC) are intractable to various treatment schemes. Bevacizumab as a novel anti-VEGF drug, its safety for these two high-risk breast cancers remains controversial. Therefore, we conducted this meta-analysis to assess the safety of Bevacizumab for TNBC and HER-2 negative MBC. Methods: We searched Medline, Embase, Web of science and Cochrane databases updated to 1 Oct 2022 for relevant randomized controlled trials (RCTs). In all, 18 RCTs articles with 12,664 female patients were included. We used any grade Adverse Events (AEs) and grade ≥3 AEs to assess the AEs of Bevacizumab. Results: Our study demonstrated that the application of Bevacizumab was associated with increased incidence of grade ≥3 AEs (RR = 1.37, 95% CI 1.30–1.45, Rate: 52.59% vs. 41.32%). Any grade AEs (RR = 1.06, 95% CI 1.04–1.08, Rate: 64.55% vs. 70.59%) did not show a significant statistical difference in both overall results and among the subgroups. In subgroup analysis, HER-2 negative MBC (RR = 1.57, 95% CI 1.41–1.75, Rate: 39.49% vs. 25.6%), dosage over 15 mg/3w (RR = 1.44, 95% CI 1.07–1.92, Rate: 28.67% vs. 19.93%) and endocrine therapy (ET) (RR = 2.32, 95% CI 1.73–3.12, Rate: 31.17% vs. 13.42%) were associated with higher risk of grade ≥3 AEs. Of all graded ≥3 AEs, proteinuria (RR = 9.22, 95%CI 4.49–18.93, Rate: 4.22% vs. 0.38%), mucosal inflammation (RR = 8.12, 95%CI 2.46–26.77, Rate: 3.49% vs. 0.43%), palmar-plantar erythrodysesthesia syndrome (RR = 6.95, 95%CI 2.47–19.57, Rate: 6.01% vs. 0.87%), increased Alanine aminotransferase (ALT) (RR = 6.95, 95%CI 1.59–30.38, Rate: 3.13% vs. 0.24%) and hypertension (RR = 4.94, 95%CI 3.84–6.35, Rate: 9.44% vs. 2.02%) had the top five risk ratios. Conclusion: The addition of Bevacizumab for TNBC and HER-2 negative MBC patients showed an increased incidence of AEs especially for grade ≥3 AEs. The risk of developing different AEs varies mostly dependent on the type of breast cancer and combined therapy. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022354743].

Project description:BackgroundThe tropomyosin receptor kinase (TRK) pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse events (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial.Patients and methodsPatients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized.ResultsNinety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% [95% confidence interval (CI), 43%-62%] of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with glucagon-like peptide 1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%-51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%-46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor reinitiation was the most effective intervention for withdrawal pain.ConclusionsTRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.

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An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

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An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

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