Renal%20cancer Treatment

• To reduce mortality and remission
• To prevent complications

Adjuvant Therapy

• Sunitinib is the only approved adjuvant therapy option for patients at high risk for recurrence based on the Sunitinib Treatment of Renal Adjuvant Cancer (S-TRAC) trial
  • Indicated for patients with stage III clear cell renal cell carcinoma (ccRCC) with high risk for relapse
• Adjuvant Pembrolizumab may be considered in intermediate- to high-risk operable ccRCC patients, with treatment initiated within 12 weeks post-op and to continue for up to 1 year

Cancer Immunotherapy/Immunomodulating Agents

Aldesleukin or Interleukin-2 (IL-2)

• Modified form of interleukin-2 produced by recombinant DNA technology
• Promotes proliferation, differentiation and recruitment of T and B cells, natural killer (NK) cells and thrombocytes
• High-dose IL-2 is recommended as 1st-line therapeutic option for highly selected patients with relapsed or medically unresectable stage IV predominantly ccRCC, depending on patient's prognostic risk for use under certain circumstances
  • Also used as a subsequent therapy option for select clear cell stage IV RCC patients with excellent performance status and normal organ function

Interferon-α (IFN-α)

• Possesses antiviral, antiproliferative and immunomodulatory effects, and promotes cellular differentiation,regulation of cell surface major histocompatibility antigen expression and cytokine induction
• Use in ccRCC has been largely replaced with targeted therapeutic agents and checkpoint inhibitors

Systemic Therapy

Axitinib

• Second-generation, potent tyrosine kinase inhibitor that selectively targets vascular endothelial growth factors (VEGF) 1, 2 and 3 and inhibits angiogenesis, metastasis and tumor growth
• Used as 1st-line treatment option for patients with relapsed or medically unresectable predominantly clear cell and non-clear cell stage IV RCC for use under certain circumstances and as subsequent therapy option after failure prior systemic therapy

Axitinib + Avelumab

• Avelumab is a human IgG1 lambda monoclonal antibody that binds to the programmed death ligand-1 (PD-L1) found on T-cells and blocks the interaction of PD-L1 with PD-1 and B7.1 receptors on the tumor cell
• Alternative option for 1st-line therapy of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC
• Used as subsequent treatment option for patients with relapsed or medically unresectable ccRCC after treatment failure with 1st-line medications

Axitinib + Pembrolizumab

• Pembrolizumab is a PD-1 blocking monoclonal antibody that works by preventing the interaction between PD-1 and the PD-L1 and PD-L2 ligands
• Preferred option for 1st-line treatment of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC
• Used as subsequent treatment option for patients with relapsed or medically unresectable ccRCC after treatment failure with 1st-line medications

Belzutifan

• A hypoxia-inducible factor 2α (HIF-2α) inhibitor that blocks the heterodimerization of HIF-2α with HIF-2β, thereby inducing tumor regression
• May be used as subsequent therapy option for the treatment of VHL-associated RCC not requiring immediate surgery

Bevacizumab

• Recombinant humanized monoclonal antibody that binds to VEGF that inhibits angiogenesis occurring during the growth of the tumor
• May be used as subsequent therapy option for predominantly clear cell stage IV RCC after prior cytokine therapy
• Treatment option for patients with non-clear cell RCC for use under certain circumstances
• Approved biosimilars (eg Bevacizumab-awwb, Bevacizumab-bvzr) may be used in place of Bevacizumab

Bevacizumab + Erlotinib

• May be considered for select patients with advanced papillary RCC, including HLRCC-associated RCC

Bevacizumab + Everolimus

• Recommended for select patients with advanced RCC with non-clear cell RCC

Bevacizumab + IFN-α

• Based from the AVOREN (phase III) double-blind trial, the addition of Bevacizumab to IFN-α significantly increases progression-free survival (PFS)

Cabozantinib

• A small-molecule inhibitor of tyrosine kinases such as VEGFRs, MET and AXL 
• Preferred 1st-line treatment option of poor- and intermediate-risk patients with relapsed or medically unresectable predominantly clear cell stage IV RCC and relapsed or stage IV non-clear cell RCC
• Alternative option for 1st-line treatment of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC with favorable-risk features
• Also used as preferred subsequent therapy option for predominantly clear cell stage IV RCC
• According to the results of an interim analysis of the Phase III METEOR trial, it has significantly delayed the progression of the disease as compared with Everolimus in patients with advanced clear cell renal cell carcinoma (ccRCC) with prior VEGR-TKI treatment
• The trial results showed that Cabozantinib was able to shrink the tumors and slow down the tumor growth

Cabozantinib + Nivolumab

• Preferred option for 1st-line treatment of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC
• Used as subsequent treatment option for patients with relapsed or medically unresectable ccRCC after treatment failure with 1st-line medications 
• Used as a treatment option for patients with relapsed or medically unresectable non-clear cell stage IV RCC
• CheckMate 9ER study results showed superior progression-free survival and response rates with significant overall survival advantages for Cabozantinib and Nivolumab combination therapy irrespective of IMDC prognostic subgroups and PD-L1 biomarker status

Erlotinib

• An oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recommended as 1st-line treatment option for patients with relapsed or medically unresectable stage IV non-clear cell RCC, for use under certain circumstances

Everolimus

• A macrolide immunosuppressant and analog of Sirolimus that inhibits mammalian target of Rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway 
• Used as alternative for subsequent treatment of predominantly advanced ccRCC after treatment failure with 1st-line medications
  • The RECORD-1 trial results revealed that Everolimus can be safely given to patients with previous intolerance to vascular endothelial growth factor receptors-tyrosine kinase inhibitor (VEGFr-TKI) therapy
• May be considered as a treatment option for non-clear cell RCC patients 
• May be considered for patients with TSC-associated RCC

Everolimus + Lenvatinib

• Lenvatinib is a multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3 and other kinases involved in pathogenic angiogenesis, tumor growth and cancer progression 
• Combination regimen used as a subsequent therapy option for predominantly clear cell stage IV RCC and as a treatment option for non-clear cell RCC

Ipilimumab + Nivolumab

• Ipilimumab is a monoclonal antibody that binds to cytotoxic T-lymphocyte antigen 4 (CTLA-4) therebyblocking CTLA-4 interactions with its ligands
• Preferred combination treatment for 1st-line therapy for intermediate- and poor-risk patients with previously untreated, relapsed or medically unresectable, predominantly clear cell stage IV renal cancer
• For favorable-risk patients, this combination is considered as a treatment option for 1st-line treatment
• Also used as one of the preferred subsequent treatment regimen for patients with predominantly advanced ccRCC after treatment failure with 1st-line medications
• May be used as 1st-line treatment for patients with predominantly sarcomatoid non-clear cell RCC

Lenvatinib + Everolimus

• Used as subsequent treatment option for patients with relapsed or medically unresectable stage IV ccRCC after treatment failure with 1st-line medications
• Used as a treatment option for patients with relapsed or medically unresectable non-clear cell stage IV RCC

Lenvatinib + Pembrolizumab

• Preferred option for 1st-line treatment of patients with relapsed or medically unresectable stage IV ccRCC
• Used as subsequent treatment option for patients with relapsed or medically unresectable ccRCC after treatment failure with 1st-line medications

Nivolumab

• A human programmed death receptor-1 (PD-1) blocking antibody used in patients who already received angiogenesis inhibitor therapy
• Preferred agent for the subsequent treatment of patients with predominantly clear cell stage IV RCC and treatment option of select patients with advanced non-clear cell RCC

Pazopanib

• An oral angiogenesis inhibitor that targets the VEGFR-1, -2, and -3, platelet-derived growth factor receptors (PDGFR-α and -β) and stem cell factor receptor (c-KIT)
• Alternative option for 1st-line treatment of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC with favorable and poor- to intermediate-risk features 
• May be considered in patients with relapsed or medically unresectable stage IV non-clear RCC under certain circumstances
• Also used as alternative subsequent therapy option for patients unresponsive to 1st-line therapy regimens
• May be considered for patients with VHL-associated RCC
• It is important to monitor the liver function tests (LFTs) before and during treatment with Pazopanib

Pembrolizumab

• Treatment option for stage IV or relapsed non-clear cell RCC patients

Savolitinib

• A MET tyrosine kinase inhibitor currently undergoing clinical studies for its use as 1st-line treatment of MET-driven tumors
• May be considered as a 2nd-line option for advanced/metastatic MET-driven papillary RCC

Sorafenib

• Small molecule that inhibits multiple isoforms of the intracellular serine/threonine kinase, RAF and also other receptor tyrosine kinases, including VEGFR-1, -2, and -3, PDGFR-β, FMS-like tyrosine kinase (FLT-3), c-KIT and neurotrophic factor receptor (RET)
• Used as subsequent therapy option for patients unresponsive to 1st-line therapy other than Sorafenib depending on patient circumstances

Sunitinib

• Multikinase inhibitor targeting several tyrosine kinase inhibitors that is implicated in PDGFR-α and -β, VEGFR-1, -2, and -3, c-KIT, FLT-3, colony-stimulating factor (CSF-1R) and RET
• Treatment option for 1st-line therapy of patients with relapsed or medically unresectable predominantly clear cell stage IV RCC with favorable or poor- to intermediate-risk features, and as alternative subsequent therapy option for patients unresponsive to 1st-line therapy other than Sunitinib
• Also used as an adjuvant therapy option for patients with clear cell localized RCC at high risk for disease recurrence 
• Also recommended as preferred treatment option for stage IV or relapsed non-clear cell RCC patients

Temsirolimus

• Inhibitor of the mTOR protein that regulates micronutrients, cell growth, apoptosis and angiogenesis by its downstream effects on a variety of proteins
• Alternative option for 1st-line treatment of poor-risk patients with relapsed or medically unresectable predominantly clear cell stage IV RCC to be used under certain circumstances
• May be used as subsequent therapy option for predominantly clear cell stage IV RCC after prior cytokine therapy
• Recommended 1st-line treatment option for non-clear cell RCC patients with poor prognosis

Tivozanib

• A selective VEGF tyrosine kinase inhibitor approved in European countries as alternative 1st-line treatment for patients with ccRCC with favorable risk factors
• Used as subsequent treatment option for patients with relapsed or medically unresectable ccRCC after treatment failure with ≥2 prior systemic therapies

Recommended Chemotherapeutic Agents for Metastatic RCC

• Treatment with Gemcitabine + Doxorubicin or Sunitinib may be considered in patients with sarcomatoid RCC
• Gemcitabine with Carboplatin or Cisplatin and Paclitaxel with Carboplatin may be used for patients with other non-clear cell subtypes

• Bone-modifying agents (eg bisphosphonates, RANK-L inhibitor Denosumab) and supplementation with vitamin D and calcium are recommended for RCC patients with bone metastases and creatinine clearance ≥30 mL/min
  • Bisphosphonate therapy with Zoledronic acid has been shown to reduce skeletal-related events in patients with bone metastases

Stereotactic Body Radiation Therapy (SBRT)

• Recommended in patients with poor prognosis or those with unsuitable clinical condition
• May be considered for patients with medically inoperable stage I-III disease 
• Conventional and stereotactic RT are frequently useful to treat a single or limited number of metastases
• Effective therapy for the palliation of local and symptomatic metastatic disease
• Prevents the progression of metastatic disease in critical sites: Bones and brain

Whole Brain Irradiation

• Recommended for patients with multiple brain metastasis