There has been significant discoveries in the genomics of these RCC entities, especially from the TCGA data. These include MET alterations in papillary RCC type 1, the discovery of NRF2-ARE, and CDKN2S loss in papillary RCC type 2, in chromophobe RCC - finding out that mtDNA is a component of disease biology, and recurrent breakpoints in TERT promoter. In sarcomatoid RCC – discovering that CDKN2A GA could be associated with CDK4/6 inhibitor sensitivity, and that NF2 Gas could be associated with everolimus sensitivity.
Most previous clinical trials grouped all nccRCC subtypes into the same trial group. Examples include the ESPN trial including all subtypes of metastatic nccRCC, comparing Sunitinib to Everolimus and then performing a crossover on progression. However, the number of patients in this trial was arguably quite low to make significant conclusions. Two additional similar trials were the RECORD-3 and ASPEN trials, including the same type of patients and same drug comparison, demonstrating similar results. All 3 trials showed that patients with Sunitinib did better than those who received Everolimus.
Dr. Pal suggested the usage of rationally selected drugs for each nccRCC subtype in a specific manner. He focused on papillary RCC as an example, showing that MET inhibition in this specific subtype is potentially uniquely beneficial. Therefore, Dr. Pal is now leading a new trial, the SWOG 1500 only for metastatic papillary RCC, randomizing patients into 4 arms: Sunitinib, Cabozantinib, Crizotinib and Savolitinib. Another new randomized trial, led by Dr. T. Choueiri, will randomize the same unique patients to either Savolitinib or Sunitinib.
Dr. Pal also mentioned the many ongoing clinical trials are trying to ascertain the role of potentially beneficial immunotherapy, specifically in nccRCC subtypes. One of these new randomized clinical trials is the SUO-CTC trial, recruiting patients with either high risk or metastatic clear cell/sarcomatoid RCC, and randomizing them to placebo or Atezolizumab.
In summary, Dr. Pal reiterated the idea that emerging studies on nccRCC should use targeted drugs and/or immunotherapies in relevant nccRCC subtypes.
Presented By: Sumanta K. Pal, MD, City of Hope Comprehensive Cancer Center
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA