AimBevacizumab and ramucirumab are antiangiogenic monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, used in various cancers. Bleeding events have been described with these two agents. We conducted an up-to-date meta-analysis to determine the relative risk (RR) associated with the use of antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab.MethodsThis meta-analysis of randomized controlled trials was performed after searching PubMed, American Society for Clinical Oncology Abstracts, European Society for Medical Oncology Abstracts, and the proceedings of major conferences for relevant clinical trials. RR and 95% CIs were calculated by random-effects or fixed-effects models for all-grade and high-grade bleeding events related to the angiogenesis inhibitors.ResultsEighty-five randomized controlled trials were selected for the meta-analysis, covering 46,630 patients. The results showed that antiangiogenic monoclonal antibodies significantly increased the risk of all-grade (RR: 2.38, 95% CI: 2.09–2.71, p<0.00001) and high-grade (RR: 1.71, 95% CI: 1.48–1.97, p<0.00001) bleeding compared with control arms. In the subgroup analysis, bevacizumab significantly increased the risk of all-grade (RR: 2.73, 95% CI: 2.24–3.33, p<0.00001) and high-grade bleeding (RR: 1.98, 95% CI: 1.68–2.34, p<0.00001), but ramucirumab only increased the risk of all-grade bleeding (RR: 1.94, 95% CI: 1.76–2.13, p<0.00001) and no difference was observed for the risk of high-grade bleeding (RR: 1.04, 95% CI: 0.78–1.39, p=0.79) compared with the control group. For lung cancer patients, bevacizumab significantly increased the risk of all-grade (RR: 4.72, 95% CI: 1.99–11.19, p=0.0004) and high-grade pulmonary hemorrhage (RR: 3.97, 95% CI: 1.70–9.29, p=0.001), but no significant differences in the risk of all-grade (RR: 1.09, 95% CI: 0.76–1.57, p=0.64) and high-grade (RR: 1.22, 95% CI: 0.35–4.21, p=0.75) pulmonary hemorrhage were observed for ramucirumab. The increased risk of all-grade and high-grade bleeding was also observed in colorectal cancer or non-colorectal tumors and low-dose or high-dose angiogenesis inhibitors.ConclusionAntiangiogenic monoclonal antibodies are associated with a significant increase in the risk of all-grade and high-grade bleeding. Ramucirumab may be different from bevacizumab in terms of the risk of high-grade bleeding and the risk of all-grade and high-grade pulmonary hemorrhage in lung cancer patients.
Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR-TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.
Background: To survey the prevalence of potential drug-drug interactions (DDIs) between anticancer drugs and non-anticancer drugs and evaluate the risk factors associated with these drug-drug interactions in China. Methods: All discharged patients in the Department of Oncology were collected from Jun to Dec in 2016 with the Hospital Information System of the Chinese people’s Liberation Army General Hospital. Drugs were screened for interactions by Micromedex solutions database. Descriptive statistics were generated and logistic regression was used to identify the associated factors. Results: Among 6578 eligible patients, 1979 potential drug interactions were found in 1830 patients (27.82%). The most common drug-drug interaction was cisplatin and furosemide. Erlotinib was most likely to interact with various non-anticancer drugs. Most interactions were classified as pharmacodynamics (71.60%), major severity (97.02%) and were supported by fair documentation evidence (86.21%). In multivariate analysis, increasing number of medications, lung cancer and patients with stage IV had a higher risk for potential drug-drug interactions. Conclusion: Potential drug-drug interactions between antineoplastic drugs and non-antineoplastic drugs occur frequently in cancer patients of Chinese hospitals. Doctors should fully consider potential risk associated with DDIs. Further research should be performed to evaluate real clinical significance of these drug-drug interactions.
Context: Hypertension events are the dominant adverse events observed in patients receiving the antivascular endothelial growth factor (anti-VEGF) monoclonal antibodies bevacizumab and ramucirumab treatment, which severe hypertension, particularly hypertensive emergencies, may cause acute target organ injury and major cardiovascular events, that has limited the administration of anti-VEGF monoclonal antibodies. The current meta-analysis aimed to examine the relative risk (RR) of hypertension associated with anti-VEGF monoclonal antibodies. Evidence Acquisition: PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library, and Clinical Trials.gov were searched until July 2019 for relevant phase II and III randomized controlled trials (RCTs). Statistical analyses were performed to examine the RR (with 95% confidence intervals (CIs)) of hypertension associated with the anti-VEGF monoclonal antibodies. Results: Ninety four RCTs and 51088 patients were included in the current meta-analysis. According to the results, compared with the control arms, anti-VEGF monoclonal antibodies increased the risk of all-grade (RR: 3.45, 95% CI: 2.98 - 4.00) and high-grade (RR: 5.63, 95% CI: 5.05 - 6.26) hypertension. In the subgroup analyses, the risk of high-grade hypertension varied significantly with cancer type, so that the highest RR was for patients with ovarian cancer (17.27, 95% CI: 8.50 - 35.08), whereas the risk of all-grade hypertension did not vary significantly. When stratified based on drug types and drug dose, no significant difference was discovered. Conclusions: Anti-VEGF monoclonal antibodies significantly increased the risk of hypertension. The risk may vary with tumor type. Clinicians should be aware of the adverse reaction and clinical monitoring as well as effective management of such situations, particularly for high-risk patients.
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