Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small cell lung cancer

Akerley, Wallace; Langer, Corey J.; Oh, Yun Kyu; Strickland, Dudley K.; Royer, Sabrina; Xia, Qing; Mu, Yuxin; Huang, Jie; Socinski, Mark A.

doi:10.1200/jco.2008.26.15_suppl.8043

Cited by 32 publications

(31 citation statements)

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“…Although there were previous safety concerns regarding the use of bevacizumab in patients with brain metastases, the incidence of ICH in this study was low and similar to historical controls in NSCLC without brain metastases, although direct cross-trial comparisons should be viewed with caution (30)(31)(32). One could hypothesise that the small lesions described in the study (mean size, 13 mm) might be less likely to bleed or perhaps have less intracranial edema.…”

Section: Discussionmentioning

confidence: 82%

“…Retrospective analyses of patients with NSCLC and treated brain metastases in the ATLAS and PASSPORT studies reported no grade >2 hemorrhages (n ¼ 85; ref. 32). A recent evidence-based review was carried out on the risk of CNS hemorrhage in patients with NSCLC receiving anti-VEGF therapy, which concluded that there was no significantly increased risk of CNS hemorrhage associated with anti-VEGF therapy (33).…”

Section: Discussionmentioning

confidence: 99%

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Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Besse

Moulec

Mazières

et al. 2015

Clinical Cancer Research

197

120

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Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-na€ ve or pretreated patients with nonsmall cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve Â6) and paclitaxel (200 mg/m 2 ) every 3 weeks (B þ CP), or second-line bevacizumab plus erlotinib (150 mg/d; B þ E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B þ CP) or more than two (B þ E) intracranial hemorrhages.Results: In first-line B þ CP cohort (n ¼ 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n ¼ 24), efficacy results for the second-line B þ E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Besse

Moulec

Mazières

et al. 2015

Clinical Cancer Research

197

120

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“…Intracerebral hemorrhage (ICH) is a particular concern with VEGFI toxicity because of the high likelihood of fatality; however, evidence is lacking in the metastatic setting because patients with brain metastases have largely been excluded from phase II and phase III clinical trials. Small studies have reported a low likelihood of central nervous system (CNS) hemorrhage [56]; however, major CNS bleeding has been reported in a handful of patients treated with either sorafenib, bevacizumab, or sunitinib [50], and it is prudent to offer VEGFI therapy to patients with stable brain metastases and after local measures (radiotherapy with or without surgery) have been undertaken. Higher mortality from ICH was reported in patients on sunitinib or sorafenib, but this may have been related to the effects of uncontrolled hypertension rather than hemorrhage per se [57].…”

Section: Clinical Manifestations and Managementmentioning

confidence: 99%

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

et al. 2011

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Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities.Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/ Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. The Oncologist 2011;16:432-444

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“…PASSPORT is a phase II study to assess bevacizumab in combination with first-or second-line chemotherapy in patients with nonsquamous NSCLC and brain metastases. An early analysis including 85 bevacizumab-treated NSCLC patients with brain metastases in the ATLAS and PASSPORT trials has recently been reported [41]. In this cohort, no CNS hemorrhages occurred during bevacizumab treatment and a single grade 2 CNS bleed was observed during postprogression therapy.…”

Section: Bevacizumab In Patients With Brain Metastasesmentioning

confidence: 92%

Antiangiogenic treatments of advanced non-small cell lung cancer

Manegold

2008

Targ Oncol

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Over the past decades, chemotherapy regimens have only offered moderate improvements in survival to patients with advanced or metastatic non-small cell lung cancer (NSCLC). The advent of targeted therapies, which selectively inhibit tumor-specific biological pathways, heralds a new era for cancer care. Targeting vascular endothelial growth factor (VEGF)-a potent regulator of tumor angiogenesis-is now considered to be a rational anticancer strategy. Bevacizumab is a monoclonal antibody that specifically inhibits VEGF. In large, randomized, phase III trials, bevacizumab-based therapy demonstrated significant improvements in patient outcomes coupled with a favorable safety profile in non-squamous NSCLC. The results of the numerous ongoing studies concerning the use of bevacizumab in other histological types and in previously ineligible patient populations, its optimal combination with other targeted therapies, and the potential of bevacizumab in earlier-stage disease, are eagerly awaited.

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Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small cell lung cancer

Cited by 32 publications

References 0 publications

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

Antiangiogenic treatments of advanced non-small cell lung cancer

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