Bevacizumab and risk of intracranial hemorrhage in patients with brain metastases: a meta-analysis

Yang, Lin; Chen, Chuan-Jie; Guo, Xiaolu; Wu, Xiling; Lv, Bo-Jie; Wang, Hongli; Guo, Zhi; Zhao, Xinjin

doi:10.1007/s11060-017-2693-4

Cited by 25 publications

(17 citation statements)

References 40 publications

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“…Finally, targeting CSPG4-positive GMB-associated vasculature could result in acute cranial hemorrhage, with potentially lethal consequences. Clinical data obtained from GBM patients receiving the anti-angiogenetic agent bevacizumab did not reveal a significant risk of bleeding [38]. However, owing to the different functional properties and potencies of CAR-T cells and monoclonal antibodies, direct comparisons and extrapolations are difficult.…”

Section: Cspg4-car-t-cell Therapy Of Different Tumorsmentioning

confidence: 99%

“…At the protein level, nonetheless, CSPG4 expression seems to be confined to the small intestine [34]. Moreover, CSPG4 displays a broad expression across several different cancer entities, such as melanoma [35], leukemia [36], glioma [37], triple-negative breast cancer [38], head and neck cancers [39], and mesenchymal cancers [40]. In the present review, we want to shine the light on CSPG4 as a promising target antigen for CAR-T-cell therapy.…”

Section: Introductionmentioning

confidence: 99%

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CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities–Merits and Challenges

Harrer

Dörrie

Schaft

2019

IJMS

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Targeting cancer cells using chimeric-antigen-receptor (CAR-)T cells has propelled adoptive T-cell therapy (ATT) to the next level. A plentitude of durable complete responses using CD19-specific CAR-T cells in patients suffering from various lymphoid malignancies resulted in the approval by the food and drug administration (FDA) of CD19-directed CAR-T cells for the treatment of acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). A substantial portion of this success in hematological malignancies can be traced back to the beneficial properties of the target antigen CD19, which combines a universal presence on target cells with no detectable expression on indispensable host cells. Hence, to replicate response rates achieved in ALL and DLBCL in the realm of solid tumors, where ideal target antigens are scant and CAR-T cells are still lagging behind expectations, the quest for appropriate target antigens represents a crucial task to expedite the next steps in the evolution of CAR-T-cell therapy. In this review, we want to highlight the potential of chondroitin sulfate proteoglycan 4 (CSPG4) as a CAR-target antigen for a variety of different cancer entities. In particular, we discuss merits and challenges associated with CSPG4-CAR-T cells for the ATT of melanoma, leukemia, glioblastoma, and triple-negative breast cancer.

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Section: Cspg4-car-t-cell Therapy Of Different Tumorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities–Merits and Challenges

Harrer

Dörrie

Schaft

2019

IJMS

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“…Generally, the side effects of BEV therapy include hemorrhage/bleeding, wound healing complications, gastrointestinal perforation, arterial thromboembolism, congestive heart failure, hypertension, proteinuria/ nephrotic syndrome, infusion-related hypersensitivity reactions, and reversible posterior leukoencephalopathy syndrome [40,41]. A meta-analysis of eight studies found that BEV treatment was not associated with a significant increase in intracerebral hemorrhage in cancer patients with BM [13]. In this study, the CNS bleeding rate with BEV treatment in NSCLC patients was 1%, which suggests that the risk of intracerebral hemorrhage is low with BEV treatment.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of 24 randomized controlled trials found that BEV treatment improved the overall survival (OS) and PFS in patients with metastatic solid tumors but was associated with a statistically higher incidence of fatal adverse events (AEs) overall and an increased risk of fatal pulmonary hemorrhage in patients with lung cancer [12]. However, a meta-analysis of cancer patients with BM found that BEV treatment was not associated with a significantly increased risk of intracerebral hemorrhage [13].…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis

et al. 2020

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AbstractThis study evaluates the efficacy and safety of bevacizumab (BEV) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BM) by performing meta-analyses of response and survival indices. Seventeen studies were included. BEV treatment was associated with a lower new BM incidence (hazard ratio: 0.30 [95% confidence interval (CI): 0.14, 0.46]) during follow-up. Disease control rate (DCR) of BEV-treated patients with BM was 91% [95% CI: 85, 95]. However, intracranial DCR was relatively higher (94% [95% CI: 87, 98]) than extracranial DCR (86% [95% CI: 74, 96]). DCR of NSCLC patients with BM was significantly better with BEV than with control therapies (odds ratio: 2.71 [95% CI: 1.26, 5.86], P = 0.01). Progression-free survival (PFS) of BEV-treated patients with and without BM was 7.1 months [95% CI: 6.2, 8.0] and 7.4 months [95% CI: 6.3, 8.4], respectively. Intracranial PFS of BEV-treated patients with BM was 8.0 months [95% CI: 6.0, 10.0]. Overall survival of BEV-treated NSCLC patients with and without BM was 13.5 months [95% CI: 11.4, 15.6] and 12.5 months [95% CI: 10.2, 14.8], respectively. The incidence of bleeding/hemorrhage in the central nervous system was 1% with BEV treatment.

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“…Concerns regarding a potential association with risk of intracranial hemorrhage have discouraged the use of bevacizumab 33 . Yet, there have been studies of patients with primary brain tumors reporting clinical benefit and no significant increase in intracranial hemorrhage 34 , and a meta-analysis of eight studies covering 8,713 patients demonstrated no increase in the risk of intracranial hemorrhage in patients with brain metastases 35 .…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab for the treatment of non-small cell lung cancer patients with synchronous brain metastases

Ascha

Wang

Kumthekar

et al. 2019

Sci Rep

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Bevacizumab is FDA-approved in the treatment of primary brain tumors, but its efficacy in patients with brain metastases could be better-studied. This study examines a population of non-small cell lung cancer (NSCLC) patients with synchronous brain metastases to identify predictors of the decision to use bevacizumab and survival following bevacizumab treatment. Primary cancer registry data were used to determine which NSCLC patients diagnosed in the years 2010 through 2012 had synchronous brain metastases at the time of diagnosis, and Medicare claims used to identify a population of patients treated with bevacizumab. Record of bevacizumab treatment was found for 81 and 666 patients with and without brain metastases, respectively. After adjusting for clinical and demographic characteristics, bevacizumab was associated with 0.88 times the hazard of mortality in the elderly NSCLC population (95% CI: 0.81–0.96, p: 0.003) and a corresponding hazard ratio of 0.75 in the population of elderly NSCLC patients with synchronous brain metastases (95% CI: 0.59–0.96, p: 0.020). Bevacizumab may benefit NSCLC patients with synchronous brain metastases more than it does patients without intracranial disease, possibly as a result of its multiple potential mechanisms of action simultaneously inhibiting angiogenesis and minimizing vasogenic edema.

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Bevacizumab and risk of intracranial hemorrhage in patients with brain metastases: a meta-analysis

Cited by 25 publications

References 40 publications

CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities–Merits and Challenges

CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities–Merits and Challenges

Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis

Bevacizumab for the treatment of non-small cell lung cancer patients with synchronous brain metastases

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