PURPOSE OF REVIEW: Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC. RECENT FINDINGS: The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib-gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes. SUMMARY: Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto-oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design.
PURPOSE OF REVIEW: Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC. RECENT FINDINGS: The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib-gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes. SUMMARY: Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto-oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design.
Authors: Martin H Voss; Ana M Molina; Ying-Bei Chen; Kaitlin M Woo; Joshua L Chaim; Devyn T Coskey; Almedina Redzematovic; Patricia Wang; William Lee; S Duygu Selcuklu; Chung-Han Lee; Michael F Berger; Satish K Tickoo; Victor E Reuter; Sujata Patil; James J Hsieh; Robert J Motzer; Darren R Feldman Journal: J Clin Oncol Date: 2016-11-10 Impact factor: 44.544
Authors: Chung-Han Lee; Martin H Voss; Maria Isabel Carlo; Ying-Bei Chen; Mark Zucker; Andrea Knezevic; Robert A Lefkowitz; Natalie Shapnik; Chloe Dadoun; Ed Reznik; Neil J Shah; Colette Ngozi Owens; Deaglan Joseph McHugh; David Henry Aggen; Andrew Leonard Laccetti; Ritesh Kotecha; Darren R Feldman; Robert J Motzer Journal: J Clin Oncol Date: 2022-03-17 Impact factor: 50.717