Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Powles, Thomas; Sarwar, Naveed; Stockdale, Andrew; Sarker, Shah-Jalal; Boleti, Ekaterini; Protheroe, Andrew; Jones, Robert J.; Chowdhury, Simon; Peters, John; Oades, Grenville; O’Brien, Tim; Sullivan, M.; Aitchison, Michael; Beltrán, Luis; Worth, Daniel C; Smith, Kate; Michel, Constance; Trevisan, Giorgia; Harvey-Jones, Elizabeth; Wimalasingham, Akhila; Sahdev, Anju; Ackerman, Charlotte; Crabb, Simon J.

doi:10.1001/jamaoncol.2016.1197

Cited by 73 publications

(51 citation statements)

References 17 publications

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“…Powles and colleagues reported the outcomes of a single arm phase II study of a 102 patients with mRCC treated with pazopanib for 12-14 weeks [Powles et al 2013]. A total of 81% had SD, with 14% achieving PR.…”

Section: Tumor Downsizingmentioning

confidence: 99%

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

Borregales

Adibi

Thomas

et al. 2015

Therapeutic Advances in Urology

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Abstract:In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC.

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Section: Tumor Downsizingmentioning

confidence: 99%

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

Borregales

Adibi

Thomas

et al. 2015

Therapeutic Advances in Urology

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“…It was recently reported that the expression of programed cell death-ligand 1 (PD-L1) in the immune component increased with pazopanib therapy, while CD8 expression decreased (4). It is unclear if the same happens with sunitinib (5, 6), but it may be an explanation to justify the response achieved in our case and in the case report by Geynisman.…”

Section: Background and Discussionmentioning

confidence: 99%

Long-term Response to Nivolumab and Acute Renal Failure in a Patient with Metastatic Papillary Renal Cell Carcinoma and a PD-L1 Tumor Expression Increased with Sunitinib Therapy: A Case Report

et al. 2016

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IntroductionPapillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma.Case reportWe describe a case of a young man diagnosed with PRCC that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To the best of our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal cell carcinoma patient.Concluding remarksNivolumab is a promising drug in patients with metastatic PRCC and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

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“…The results of single-agent phase 2 clinical trials with neoadjuvant anti-angiogenic agents (e.g., vascular endothelial growth factor receptor tyrosine kinase inhibitors [VEGFr TKI], VEGF antibodies, mammalian target of rapamycin [mTOR] inhibitors) demonstrate feasibility but not remarkable down-staging, and results with newer agents (i.e., immuno-oncology agents) will not be available in the near future. [9][10][11][12] Some patients deemed medically or surgically inoperable at diagnosis may have a dramatic radiological and/or clinical response to systemic therapy. A multidisciplinary team should re-evaluate them if there is any question that they may have converted to an operable state.…”

Section: Neoadjuvant Therapymentioning

confidence: 99%

Management of advanced kidney cancer: Canadian Kidney Cancer Forum (CKCF) consensus update 2017

North

Basappa

Bjarnason

et al. 2017

CUAJ

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Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Cited by 73 publications

References 17 publications

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

Long-term Response to Nivolumab and Acute Renal Failure in a Patient with Metastatic Papillary Renal Cell Carcinoma and a PD-L1 Tumor Expression Increased with Sunitinib Therapy: A Case Report

Management of advanced kidney cancer: Canadian Kidney Cancer Forum (CKCF) consensus update 2017

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