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 .
Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma.
Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma ( ncRCC ) compared with clear cell renal cell carcinoma ( RCC ) supports the study of combination regimens . We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC . Patients and Methods In this single-center phase II trial , treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks . The primary end point was progression-free survival ( PFS ) at 6 months . Correlative analyses explored c and i date tissue biomarkers through next-generation sequencing . Results Thirty-five patients were enrolled with the following histologic subtypes : chromophobe ( n = 5 ) , papillary ( n = 5 ) , and medullary ( n = 2 ) RCC and unclassified RCC ( uRCC , n = 23 ) . The majority of patients had papillary growth as a major component ( n = 14 ) . For 34 evaluable patients , median PFS , overall survival , and objective response rate ( ORR ) were 11.0 months , 18.5 months , and 29 % , respectively . PFS varied by histology ( P < .001 ) , and ORR was higher in patients with significant papillary ( seven of 18 ) or chromophobe ( two of five ) elements than for others ( one of 11 ) . Presence of papillary features were associated with benefit , including uRCC , where it correlated with ORR ( 43 % v 11 % ) , median PFS ( 12.9 v 1.9 months ) , and overall survival ( 28.2 v 9.3 months ; P < .001 ) . Several genetic alterations seemed to segregate by histology . In particular , somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants . All five patients achieved treatment benefit . Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features . Distinct mutational profiles among ncRCCs vary according to specific histology
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 .