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Content Update

July 30, 2019

Nivolumab plus Ipilimumab for Advanced Renal Cell Carcinoma: In April 2018, the FDA granted approvals to nivolumab and ipilimumab (Opdivo® and Yervoy®) in combination for treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma. Nivolumab is an anti-PD-1 antibody, and ipilimumab is an anti-CTLA-4 antibody. In 2015, nivolumab was approved as subsequent therapy for patients with relapsed or metastatic clear cell histology. The combination of ipilimumab and nivolumab is a NCCN category 1 first-line therapy for patients with intermediate- or poor-risk previously untreated, relapsed, or medically unresectable stage IV clear cell histology renal cell carcinoma.

KEY CONCEPTS

KEY CONCEPTS

  • Image not available. Renal cell carcinoma (RCC) predominantly occurs later in life, with about 70% of all cases diagnosed between the ages of 55 and 84 years.

  • Image not available. Established risk factors for RCC include smoking, obesity, hypertension, and inherited susceptibility.

  • Image not available. Inactivation of the von Hippel-Lindau tumor suppressor gene is the hallmark of the most common type of RCC, the clear cell histologic subtype.

  • Image not available. More than 50% of RCC cases are diagnosed by incidental findings on routine imaging for unrelated reasons.

  • Image not available. The Memorial Sloan-Kettering Cancer Center Prognostic Factors Model for Survival classifies patients into low-, intermediate-, and high-risk groups based on five clinical factors and can predict survival among both untreated patients and those treated with immunotherapy and/or targeted agents.

  • Image not available. Surgical excision of the primary tumor, either by radical or partial nephrectomy, is the preferred treatment modality for patients with stage I-III RCC, but some patients with stage IV disease may also benefit from surgery.

  • Image not available. Historically, immunotherapy (interleukin [IL]-2 and interferon [IFN]-α) was considered the preferred first-line therapy for metastatic RCC (mRCC) but has largely been replaced by targeted agents because of their improved efficacy and tolerability. Nivolumab is a new immunotherapy option for mRCC patients who have received prior targeted therapy.

  • Image not available. Sunitinib, pazopanib, and axitinib are oral small molecule inhibitors of vascular endothelial growth factor (VEGF) and platelet-derived growth factor and are treatment options as first-line therapy for mRCC. Bevacizumab and IFN-α is also a first-line option.

  • Image not available. The multikinase inhibitors sorafenib and cabozantinib, and the mammalian target of rapamycin (mTOR) inhibitor everolimus, are the oral agents used as second-line therapy options for mRCC patients who progress on a targeted therapy or cytokine-based therapy first-line regimen.

  • Image not available. Temsirolimus is an IV administered mTOR inhibitor indicated for first-line therapy in patients with high-risk mRCC.

Renal cell carcinoma (RCC) represents about 2% of all adult malignancies and is the most common type of malignancy of the kidney and renal pelvis. Until a decade ago, there were few treatment options, and those that were available had modest activity and were poorly tolerated by patients. However, treatment for the disease has been revolutionized by targeted agents that were developed based on an increased understanding of RCC pathophysiology. Clear cell is the predominant subtype of RCC (up to 75% of all cases), and is the result of inactivation of ...

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