EVIDENCE SYNTHESIS The systematic review showed an absence of evidence for treating RKCs , with data only supporting sunitinib or MET inhibitors for some specific subtypes .
PATIENT SUMMARY Patients confronted with rare kidney cancers are often treated the same way as clear-cell renal cell carcinoma patients , despite little evidence from r and omized trials .
Molecular characterization of tumors to stratify patients may improve outcomes .
CONTEXT The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas ( RCCs ) , which showed a substantial lack of evidence for management recommendations .
OBJECTIVE To improve the outcomes of patients with rare kidney cancers ( RKCs ) , we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways , involving key stakeholders with a global perspective to generate recommendations .
A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma
Lessons Learned Our results highlight additional toxicities of dual PI3K/mTOR inhibition in the clinical setting that were unforeseen from pre clinical models . Because of toxicity and lack of efficacy , BEZ235 should not be further developed in the current formulation for patients with renal cell carcinoma . Background . Allosteric inhibitors of the mammalian target of rapamycin complex 1 ( mTORC1 ) are approved for advanced renal cell carcinoma ( RCC ) . Pre clinical models have suggested that dual inhibition of phosphatidylinositol 3-kinase ( PI3 K ) and mTOR kinase may establish superior anticancer effect . We aim ed to establish safety for BEZ235 , a potent inhibitor of both PI3 K and mTOR , in advanced RCC . Methods . Patients with advanced RCC who had previously failed st and ard therapy received escalating doses of BEZ235 in sachet formulation twice daily until progression or unacceptable toxicity . Primary endpoints were to identify the maximally tolerated dose ( MTD ) and to determine the recommended dose for the phase II study . Results . The study was terminated early because of high incidence of dose-limiting toxicities ( DLTs ) across all dose levels tested . Ten patients were treated with BEZ235—six  with clear cell and four with non-clear cell subtypes . Five of these patients suffered DLTs : 2 of 2 patients in the original 400 mg b.i.d . cohort , 1 of 6 in the 200 mg b.i.d . cohort , and 2 of 2 in the 300 mg b.i.d . cohort . DLTs included fatigue , rash , nausea and vomiting , diarrhea , mucositis , anorexia , and dysgeusia .  Five patients were evaluable for response : Two had stable disease as best response , and three had progressive disease . Conclusion . BEZ235 twice daily result ed in significant toxicity without objective responses ; further development of this compound will not be pursued in this disease
EVIDENCE SYNTHESIS The systematic review showed an absence of evidence for treating RKCs , with data only supporting sunitinib or MET inhibitors for some specific subtypes .
PATIENT SUMMARY Patients confronted with rare kidney cancers are often treated the same way as clear-cell renal cell carcinoma patients , despite little evidence from r and omized trials .
Molecular characterization of tumors to stratify patients may improve outcomes .
CONTEXT The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas ( RCCs ) , which showed a substantial lack of evidence for management recommendations .
OBJECTIVE To improve the outcomes of patients with rare kidney cancers ( RKCs ) , we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways , involving key stakeholders with a global perspective to generate recommendations .