Brain mets and non clear cell histology were always the exclusion criteria for most of the recent clinical trials that approved targted therapy for RCC, and treatment of those patients is currently debatable. please find and share the way you mange this group of patients
The following drug therapy is expected to be effective; Both the administration of anti-tumor cytokines such as IFN-alpha and IL-2, and the administration of molecular-targeting drugs which inhibit tyrosine kinase such as RAF, c-KIT (CD117), EGFR, HER2 etc.
And I also recommend you to read the recent literature in which demonstrates ubiquitin C-terminal hydrolase-L1 (UCHL1) abrogates the von Hippel–Lindau-mediated ubiquitination of HIF-1α, the regulatory subunit of HIF-1, and consequently promotes metastasis. The expression levels of HIF-1αand UCHL1 correlate with the clinical stage, grading and prognosis of tumor patients, which offers a rational basis for targeting the UCHL1–HIF-1 axis (deubiquitination of HIF-1α) to precent cancer metastases.
http://www.nature.com/ncomms/2015/150123/ncomms7153/full/ncomms7153.html
Tumor enucleation followed by WBRT or stereotactic ablative radiotherapy + an antiangiogenic agent as first-line.
NCT01108445: A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN) http://www.clinicaltrials.gov
Tannir NM, Jonasch E, Altinmakas E, et al. Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): A multicenter randomized phase 2 trial. ASCO Meeting Abstracts 2014; 32:4505.
I guess, the question is VERY tricky, and otherwise quet smart and addressing a huge problem..
The first trick hidden in the targeted therapy treatment of brain metastases, and the second trick is hidden in the treatment of nCC mRCC.
Luckily, as a first approach we can avoid the second part of the question, because treatment of brain metastases has very well defined rules focusing on the physical damage and removal of tumorous cells of the brain metastases. These rules gives you a well outlined guidenance depending on the size, localisation and number of brain mets considered to be treated (surgical removal, stereotactic radiosurgery, whole brain irradiation etc.).
The problem emerges as brain mets has been stabilised or the patient has metastatic lesions outside of the brain.
Very few credible information became available till this time, the luck of a well designed and well conducted phase III. randomised clinical trials is a fact. On the other hand, as Dr. Kok noted, there are few phase II results available, and lots of retrospective results with lower level of evidence. It seems to be that the preferred option is a VEGFR targeted TKI, such as sunitinib or sorafenib for the treatment of metastatic non-clear cell cancer. I'm pretty sure that new data will be also presented on the incoming GU ASCO meeting.
Trying to use an extrapolation from results of the sunitinib expanded access program, VEGFR TKIs probably able to give survival benefit for patients having stabilised brain metastases.
The treatment of these patients requires attention to both the intracranial disease and the systemic tumor. The intracranial disease management is perhaps best governed by looking at the number and size of the metastases to determine if stereotactic radiosurgery with a Gamma Knife or other delivery platform is possible. Work by Sperduto et al. (http://jco.ascopubs.org/content/30/4/419.full.pdf) showed that the number of metastases predicted survival, as did the Karnofsky Performance Status. The survival statistics for patients included in that study predate the use of the newer tyrosine kinase-targeted agents. Radiosurgery is an extremely effective tool to assure intracranial control, with up to 96% control rates reported by major centers (Sheehan JP et al. J Neurosurg 2003 Feb;98(2):342-9.). Resective therapy of brain metastases is a well-regarded therapy, but may prevent the synergy that may be possible with systemic checkpoint inhibitor therapy (nivolumab, ipilimumab, etc.). There is, as yet, no gold standard for the systemic therapy of non-clear cell renal cell carcinoma...and the therapies that have made it into our textbooks (interferon alpha and interleukin 2) will need to be tested against these targeted therapies, antiangiogenic therapies, etc., before we will have a clue on how best to treat these patients. Further molecular characterizaiton of these rarer variants of renal cell carcinoma will provide better treatment choices.