Second-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis

Larkin, James; Paine, Abby; Tumur, Indra; Cappelleri, Joseph C.; Healey, Paul J.; Foley, Grace; Mitchell, Stephen; Kroes, Michel; Chen, Connie

doi:10.1517/14656566.2013.758713

Cited by 21 publications

(10 citation statements)

References 39 publications

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“…The results of our meta-analysis also indicated that axitinib exhibits a higher efficacy and safety compared to sorafenib and pazopanib in patients who previously received systematic treatment. This finding is also in line with a recent systematic review and meta-analysis for second-line treatments in the management of advanced RCC (28). The authors of that study reported that axitinib was superior to placebo (HR=0.25, 95% CI: 0.17-0.38) or sorafenib (HR= 0.46, 95% CI: 0.32-0.68) and pazapanib (HR= 0.47, 95% CI: 0.26-0.85) in prolonging PFS.…”

Section: Discussionsupporting

confidence: 91%

Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials

Leung

Chan

Lin

2014

Molecular and Clinical Oncology

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Abstract. This network meta-analysis aimed to compare the clinical efficacy and safety among 7 newer targeted agents for the treatment of metastatic renal cell carcinoma (mRCC). All randomised clinical trials (RCTs) of targeted therapeutic drugs for mRCC were included. The study selection, data extraction and quality assessment were performed independently by two reviewers. The analysis evaluated efficacy outcomes [improvement in the median progression-free survival (PFS)] and safety outcomes (number of withdrawals due to adverse events). The network analysis included direct and indirect analyses. The quality of the selected studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. We identified 7 articles eligible for inclusion in the study. The direct comparison of the targeted agents indicated better efficacy in terms of longer PFS, but worse safety (more withdrawals due to adverse events). The indirect analysis demonstrated that axitinib was significantly more effective compared to panzopanib; sunitinib was superior to sorafenib and temsirolimus regarding efficacy outcome, without any statistically significant difference in the safety outcome. The results of the quality assessment indicated moderate scores using the GRADE method. In conclusion, the result of this network analysis suggested that sunitinib and axitinib may be more clinically efficient and axitinib is associated with a lower risk of adverse events compared to sorafenib, pazopanib and temsirolimus.

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Section: Discussionsupporting

confidence: 91%

Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials

Leung

Chan

Lin

2014

Molecular and Clinical Oncology

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“…These have been used as first-line therapy for renal cell carcinoma (RCC) and hepatocellular carcinoma worldwide and have demonstrated favorable outcomes. Recently, axitinib and pazopanib have been included as drugs that function as multikinase inhibitors; hence, multikinase inhibitors play an important role in cancer chemotherapy [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Association of Toxicity of Sorafenib and Sunitinib for Human Keratinocytes with Inhibition of Signal Transduction and Activator of Transcription 3 (STAT3)

et al. 2014

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Hand–foot skin reaction is a most common multi-kinase inhibitor-related adverse event. This study aimed to examine whether the toxicity of sorafenib and sunitinib for human keratinocytes was associated with inhibiting signal transduction and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects sorafenib- and sunitinib-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of sorafenib and sunitinib. HaCaT cells transfected with constitutively-active STAT3 (STAT3C) were resistant to the sorafenib- and sunitinib-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with sorafenib and sunitinib at low doses. Moreover, the expression of survivin and bcl-2 decreased after treatment with sorafenib and sunitinib was concomitant with variations in STAT3 activity. Sorafenib-induced STAT3 inhibition was mediated by regulation via MAPK pathways in HaCaT cells, while sunitinib-induced STAT3 inhibition was not. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in sorafenib and sunitinib-induced keratinocyte cytotoxicity.

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“…Note that, in Europe, temsirolimus is approved only ''for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) who have at least three of six prognostic risk factors'' 19 . While multiple second-line treatment options are available for mRCC, evidence for the comparative efficacy of these agents is limited 7,9,11,[20][21][22][23][24][25] . Due to the rapid emergence of multiple targeted agents within the past 8 years, comparative data from clinical trials is limited (and may never occur due to the cost of such trials).…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States

Signorovitch

Vogelzang

Pal

et al. 2014

Current Medical Research and Opinion

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Jonasch (2014) Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States, Current Medical Research and Opinion, 30:11, 2343-2353, DOI: 10.1185/03007995.2014 AbstractBackground: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study.

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Second-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis

Abstract: Results from the present study suggest that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting. Ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.

Cited by 21 publications

References 39 publications

Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials

Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials

Association of Toxicity of Sorafenib and Sunitinib for Human Keratinocytes with Inhibition of Signal Transduction and Activator of Transcription 3 (STAT3)

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States

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