Risk of Serious Neutropenic Events in Cancer Patients Treated with Bevacizumab: A Meta-analysis

Zhou, Fan; Shao, Jianghua; Wu, Lin-Quan; Yin, Xin; Yu, Xin

doi:10.7314/apjcp.2013.14.4.2453

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…The mechanism behind bevacizumab associated neutropenic events is not fully understood. Inhibition of VEGF1 receptor has been shown to block hematopoietic stem cell cycling, differentiation and recovery after bone marrow suppression 47 . Various forms of VEGF blockade by inhibition of the receptor tyrosine kinase domains or through antibodies targeting VEGF ligand, may induce myelosuppression and delay bone marrow recovery.…”

Section: Discussionmentioning

confidence: 99%

Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer

Gythfeldt

Lien

Tekpli

et al. 2020

Intl Journal of Cancer

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Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5‐fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8‐year disease‐free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.

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Section: Discussionmentioning

confidence: 99%

Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer

Gythfeldt

Lien

Tekpli

et al. 2020

Intl Journal of Cancer

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“…Bevacizumab has a well-established toxicity profile and has been associated with increased toxicity when combined with carboplatin-paclitaxel in patients with previously untreated non-squamous NSCLC, in particular toxicities associated with its anti–vascular endothelial growth factor mechanism of action [2]. A recent meta-analysis also suggested that bevacizumab treatment may increase the risk of high-grade neutropenia and febrile neutropenia [14]. Thus, the finding of increased toxicity in this cohort was not unanticipated.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study

et al. 2018

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Objectives: Platinum-based chemotherapy for advanced non–small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, ), we evaluated combinations of platinum-doublet chemotherapy with the anti–programmed death 1 monocloncal antibody pembrolizumab. Materials and methods: Patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations were randomized to pembrolizumab 2 or 10 mg/kg Q3W plus carboplatin area under the serum concentration-time curve (AUC) 6 mg/mL/min plus paclitaxel 200 mg/m2 (cohort A, any histology), carboplatin AUC 6 mg/mL/min plus paclitaxel 200 mg/m2 plus bevacizumab 15 mg/kg (cohort B, non-squamous), or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m2 (cohort C, non-squamous) for 4 cycles followed by maintenance pembrolizumab (cohort A), pembrolizumab plus bevacizumab (cohort B), or pembrolizumab plus pemetrexed (cohort C). Response was assessed by blinded independent central review. Results: Overall, 74 patients were randomized; median follow-up was 21.4, 16.4, and 17.4 months in cohorts A, B, and C, respectively. No dose-limiting toxicities occurred in any cohort at either pembrolizumab dose. Most frequent treatment-related adverse events (AEs) were alopecia, fatigue, and nausea. Treatment-related grade 3/4 AEs occurred in 40%, 42%, and 46% of patients in cohorts A, B, and C, respectively; AEs with possible immune etiology occurred in 24%, 50%, and 38% of patients, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively. Conclusion: Pembrolizumab in combination with carboplatin-paclitaxel and with pemetrexed-carboplatin yielded encouraging antitumor activity and toxicity consistent with known toxicities of platinum-based chemotherapy or pembrolizumab monotherapy.

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“…Hepatocellular carcinoma has the lowest risk of infection (RR = 0.96, 95% CI, 0.16–5.77), while gastric cancer was associated with the highest risk (RR = 2.43, 95% CI, 1.29–4.58). Another previous meta-analysis conducted by Zhou et al [23] found a significantly increased risk of high-grade neutropenia (RR 1.10, 95% CI: 1.02–1.19) and high-grade febrile neutropenia (RR 1.31, 95% CI: 1.08–1.59) in patients treated with bevacizumab. Among the 18 trials analyzed, 3 studies of NSCLC were included [9-11].…”

Section: Discussionmentioning

confidence: 95%

Risk and Incidence of Infection with Bevacizumab in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Peng

Qin

et al. 2022

Oncol Res Treat

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Background: A previous meta-analysis suggested that use of bevacizumab is associated with an increased risk of infection in cancer patients. With the continuous accumulation of evidence in non-small cell lung cancer (NSCLC), we performed a focused meta-analysis of randomized controlled clinical trials to quantify the relative risk and incidence of infectious complications in those individuals treated with bevacizumab. Methods: Electronic databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were prospective randomized clinical trials of NSCLC patients treated with bevacizumab with toxicity data on infectious complications. Relative risk (RR), overall incidence rates, and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies. Results: A total of 4,545 patients from 14 prospective RCTs (randomized controlled trials) were included for the meta-analysis. Treatment with bevacizumab was not associated with an increased risk of all grade (RR 1.12, 95% CI: 0.84 – 1.49) or high grade (RR 1.11, 95% CI: 0.86 – 1.41) infections, respectively. The summary incidences of all-grade and high-grade infection in patients receiving bevacizumab in the treatment group were 16.4% (95% CI: 15.7 – 17.2%) and 4.3% (95% CI: 3.0 – 6.1%), respectively. Conclusions: The use of bevacizumab is not associated with a significantly higher risk of infections in NSCLC patients. These data provide reassurance regarding the risk of incidence of infection in patients with NSCLC receiving bevacizumab.

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Risk of Serious Neutropenic Events in Cancer Patients Treated with Bevacizumab: A Meta-analysis

Cited by 6 publications

References 41 publications

Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer

Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study

Risk and Incidence of Infection with Bevacizumab in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

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