Update on AVOREN trial in metastatic renal cell carcinoma (mRCC): Efficacy and safety in subgroups of patients (pts) and pharmacokinetic (PK) analysis

Escudier, B.; Ravaud, Alain; Negrier, S.; Szczylik, Cezary; Molins, Joaquim Bellmunt; Bracarda, Sergio; Pisa, Pavel; Gaudreault, Jacques; Bajetta, E.

doi:10.1200/jco.2008.26.15_suppl.5025

Cited by 38 publications

(26 citation statements)

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“…In the phase III trial of carboplatin and paclitaxel with or without bevacizumab for advanced NSCLC (ECOG 4599 trial), patients receiving bevacizumab and experiencing high BP (defined as 1 or more BP reading >150/100 mm Hg or an increase >20 mm Hg from baseline) had a longer median OS from the end of the first treatment cycle (24), mRCC (21,25), and colorectal cancer (26). However, in the phase III AVOREN trial of bevacizumab combined with interferon alfa-2a for mRCC (27), grade !2 hypertension was not associated with improvements in PFS; this analysis may have been limited by the use of common toxicity criteria (CTC) grading, not actual BP measurements, and short follow-up. Analysis of a similar trial of bevacizumab combined with interferon alfa-2a for mRCC (CALGB 90206) supports the hypothesis generated here of improved clinical outcome in patients developing hypertension during therapy (28).…”

Section: Discussionmentioning

confidence: 99%

Diastolic Blood Pressure as a Biomarker of Axitinib Efficacy in Solid Tumors

Rini

Schiller

Fruehauf

et al. 2011

Clinical Cancer Research

176

120

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Purpose: To evaluate if diastolic blood pressure (dBP) !90 mm Hg during axitinib treatment is a marker of efficacy.Experimental Design: The relationship between dBP !90 mm Hg and efficacy was retrospectively explored across 5 phase II studies of single-agent axitinib for the treatment of 4 different tumor types. All patients had baseline BP 140/90 mm Hg and were stratified into 2 groups based on in-clinic BP measurements after initiating therapy: those with dBP <90 mm Hg throughout therapy and those with at least 1 dBP !90 mm Hg. Median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), and adverse events were evaluated by dBP group in individual and pooled analyses.Results: Two-hundred thirty patients were evaluated. Patients with dBP !90 mm Hg had a significantly lower relative risk of death than those with dBP <90 mm Hg [adjusted HR (95% CI) ¼ 0.55 (0.39, 0.77); P < 0.001]. The relative risk of progression was also lower in patients with dBP !90 mm Hg [HR (95% CI) ¼ 0.76 (0.54, 1.06), P ¼ 0.107], and ORR was significantly higher (43.9% vs. 12.0%; P < 0.001). In an 8-week landmark analysis, mOS (25.8 vs. 14.9 months) and mPFS (10.2 vs. 7.1 months) were greater for patients in the !90 mm Hg group. Adverse events were similar between groups.Conclusions: Axitinib efficacy correlated with dBP !90 mm Hg. Further investigation of dBP as a predictive biomarker of efficacy in patients receiving axitinib is warranted.

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Section: Discussionmentioning

confidence: 99%

Diastolic Blood Pressure as a Biomarker of Axitinib Efficacy in Solid Tumors

Rini

Schiller

Fruehauf

et al. 2011

Clinical Cancer Research

176

120

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“…Median duration of PFS was signifi cantly longer in the bevacizumab plus interferon alpha group than it was in the control group (10.2 months vs. 5.4 months; HR 0.63, p=0.0001). Increases in PFS were seen with bevacizumab plus interferon alpha irrespective of risk group or whether reduced-dose [47].…”

Section: Continuation Of Bevacizumab After Mcrc Progression To Improvmentioning

confidence: 86%

The role of antiangiogenesis therapy: Bevacizumab and beyond

Cortés

2009

Clin Transl Oncol

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The importance of angiogenesis in tumour growth and development is well known. Overexpression of vascular endothelial growth factor (VEGF), the key mediator of angiogenesis, is associated with poor prognosis in cancer. As a result, several therapeutic agents that inhibit the actions of VEGF or its receptors are currently in development for use in advanced solid tumours, such breast, colorectal, lung and renal cancer. Clinical data from trials of anti-VEGF agents in this group of tumours are discussed, with a particular focus on the efficacy and safety of bevacizumab, the anti-VEGF agent at the most advanced stage of development in those tumour types. Future potential uses of bevacizumab in cancer therapy will be discussed.

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“…High baseline serum VEGF levels have been associated with poor outcome; however it has not been shown to be useful in predicting benefit from sorafenib or bevacizumab [Escudier et al 2008;Bukowski et al 2007]. There are a number of potential biomarkers currently under investigation.…”

Section: Biomarkers Of Efficacymentioning

confidence: 99%

“…Based on randomized controlled trials published to date, an 'evidence-based' algorithm has been created to guide treatment choice. For patients with clear-cell RCC, sunitinib or bevacizumab plus interferon-a are the frontline treatments in patients with favourable or intermediate prognostic factors, and temsirolimus the first-line treatment of choice in patients with poor prognostic factors [Escudier et al 2008;Hudes et al 2007;Motzer et al 2007]. There is level 1 evidence [Harbour and Miller, 2001] for sorafenib in patients who have progressed after cytokine therapy, and everolimus is the preferred choice for patients who progress on VEGF-receptor targeted therapy.…”

Section: Introductionmentioning

confidence: 99%