Editing Metastatic Kidney Cancer (section)

== Management strategy as per the 2019 CUA Management of Advanced Kidney Cancer Consensus Statement ==

* Published before results of CHECKMATE 214
* Enrolling patients in clinical trials should always be considered the first option for patients with advanced or metastatic RCC

* '''Clear cell RCC'''

{| class="wikitable"
|'''Setting'''
|'''Patients'''
|'''Preferred'''
|'''Options'''
|-
|'''Untreated (first-line)'''
|'''Favourable-risk by IMDC'''
|'''Axitinib + Pembrolizumab^'''
|'''Sunitinib'''

'''Pazopanib***'''

'''Axitinib + Avelumab*'''

'''High-dose IL-2**'''

'''Active surveillance'''
|-
| 
|'''Intermediate/Poor-risk by IMDC'''
|'''Nivolumab + Ipilimumab'''

'''Axitinib + Pembrolizumab^'''
|'''Sunitinib'''

'''Pazopanib***'''

'''Axitinib + Avelumab^^*'''

'''Cabozantinib^^'''

'''Active surveillance'''
|-
|'''Second-line''' and beyond#
|'''Prior immune checkpoint inhibitor''' (ipilimumab, nivolumab)
|'''Cabozantinib^^^'''

'''Axitinib^^^'''
|'''Sunitinib'''

'''Pazopanib***'''

'''Lenvatinib + Everolimus^^^'''
|-
| 
|'''Prior VEGF''' (sunitnib, sorafenib, bevacizumab, pazopanib)
|'''Nivolumab'''

'''Cabozantinib'''
|'''Lenvatinib + Everolimus'''

'''Everolimus'''

'''Axitinib'''
|-
|
|Prior VEGF and immune checkpoint inhibitor
|Cabozantinib
|Sunitinib

Pazopanib

Axitinib^^

Lenvatinib + Everolimus

Everolimus
|}
'''^Not yet approved in Canada; until approval, sunitinib or pazopanib are preferred for favorable-risk and ipilimumab/nivolumab is preferred for intermediate-/poor-risk'''.

^^Not yet approved in Canada.

^^^Approved after one prior VEGF therapy only.

<nowiki>#</nowiki> If not used prior.

<nowiki>***</nowiki>Need to be monitored closely for first 12 weeks for liver toxicity

* '''First-line therapy'''
** '''Choice of initial systemic treatment is based in part on International Metastatic RCC Database Consortium (IMDC) risk status.'''
*** '''Preferred first-line therapy in'''
**** '''IMDC favourable-risk patients'''
***** '''Axitinib + pembrolizumab is the recommended treatment.'''
****** '''Avelumab/axitinib and targeted therapy with sunitinib or pazopanib can be considered as alternative active treatment options.'''
**** '''IMDC intermediate- or poor-risk patients:'''
****# '''Ipilimumab + nivolumab ('''
****#* '''Highest complete response rate ≈9%; similar to that for high-dose IL-2 (5-10%) much better than 1 % for sunitinib'''
****# '''Axitinib + pembrolizumab'''
***** Avelumab/axitinib and targeted therapy (sunitinib or pazopanib) remain alternative options, the latter especially for patients who have a contraindication to immunotherapy or who are felt to be unable to tolerate combination therapy.
** '''Active surveillance can also be considered in selected patients with one [IMDC] risk factor, as some patients have slow-growing, low-volume, and/or asymptomatic disease.'''
* '''Second-line and later therapy options'''
** '''Progression on or intolerance to first-line immune checkpoint inhibitor-based regimen'''
*** For patients who progress on, or who are intolerant of first-line immune checkpoint inhibitors, there is no prospective, randomized, phase 3 evidence available to select a preferred treatment option; options for patients in this situation include sunitinib, pazopanib, axitinib, cabozantinib, or lenvatinib/everolimus.
** '''Progression on or intolerance to first-line sunitinib or pazopanib'''
*** For patients who are intolerant to sunitinib or pazopanib, switching to the other VEGF inhibitor is a reasonable choice
*** For patients who progress on first-line sunitinib or pazopanib, preferred options are nivolumab, axitinib, or cabozantinib
*** Other evidence-based options are lenvatinib/everolimus (based on a small phase 2 study demonstrating a PFS advantage over everolimus monotherapy) or everolimus monotherapy (although found to be inferior to alternatives such as nivolumab and cabozantinib).
** '''Progression on or intolerance to prior VEGF inhibitor AND prior immune checkpoint inhibitor'''
*** For patients who progress on, or who are intolerant of, both prior VEGF inhibitor and prior immune checkpoint inhibitor, there is no evidence base available to select a preferred treatment option; options for patients in this situation include any of the options that have not previously been tried among: sunitinib, pazopanib, axitinib, cabozantinib, or lenvatinib/everolimus.

* '''Non-clear cell histology'''
** Relatively rare (constituting ≈15-25% of all kidney cancer) and have been the subject of few prospective studies.
** '''No standard therapy for non-clear-cell RCC; enrollment in clinical trial is the preferred option.'''
*** '''It is generally accepted that non-clear-cell histology patients should be treated similarly to clear-cell histology patients.'''
*** '''Clinical trials support the use of immunotherapy in this setting (nivolumab + ipilimumab; axitinib + pembrolizumab) or sunitinib if immunotherapy is not felt to be an option'''

* '''Bone modifying agents'''
** '''Can be considered for patients with bone metastases to decrease skeletal related events'''
** '''Options''':
*** '''Zoledronic acid'''
**** '''Bisphosphonate'''
**** Monthly administration is a reasonable option
**** '''Careful monitoring of renal function is required'''
**** '''Should not be given in renal dysfunction'''
*** '''Denosumab'''
**** '''Inhibitor of the receptor activator of nuclear factor kappa-B (RANK) ligand'''
** '''Patients receiving bone-modifying agents are at risk of hypocalcemia, therefore calcium and vitamin D supplements are recommended; however, paraneoplastic hypercalcemia can also occur in RCC, so monitoring of serum calcium levels is important regardless'''
** '''Patients starting on any bone-targeted therapy should ensure they have had a thorough dental history and recent dental examination prior to starting therapy, given the risk for osteonecrosis of the jaw developing.'''