San Antonio, Texas USA (UroToday.com) It is well known that no clear cell RCC comprise only a small portion of all RCC’s. Much data on the genomics of these tumors was obtained from the TCGA project. For example, papillary type 1 RCC is known to be associated with MET alterations while papillary type 2 is associated with NRF2-ARE and CDKN2A loss. Furthermore, it was shown that in sarcomatoid RCC CDKN2A alterations are associated with palbocicib sensitivity and NF2 alterations with everolimus sensitivity.
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In collecting duct RCC NF2 alterations were shown to predict everolimus sensitivity. It can be inferred from this data that the old approach of “lumping” all non-clear cell RCC together is not the correct approach. And indeed several trials examining the efficacy of non-clear cell treatments had negative results. For example the ESPN trial, which compared everolimus with sunitinib for non-clear cell RCC’s included very small number for each specific subtype (e.g. 13 and 14 papillary in each arm, 6 and 6 chromophobe). This trial did not find any difference in progression free survival between the 2 drugs. Same limitations apply to the RECORD-3 ASPEN trials.
Instead, a better approach would be to try and understand disease biology and apply the appropriate treatment. Several MET gene inhibitors were identified in recent years. Foretinib was shown to induce at least a partial response in patients with papillary RCC that were MET alteration positive. Another example is Savolitinib which is currently examined in a phase 2 trial and shows promise. Crizotinib was also shown induce at least a partial response in papillary type 1 MET positive patients. These results emphasize the need to understand MET status. Currently a SUO-CTC approved trial is attempting to compare these 3 new drugs to sunitinib. This trial will enroll 41 papillary RCC patients in each treatment arm.
Lastly, the role of PD1/PD-L1 role in non-clear histologies was reviewed. Atezolizumab (PD-L1 antibody) was not effective in non-clear RCC’s but induced a measurable response in 22% of sarcomatoid and clear cell RCC. This drug is currently examined in the adjuvant setting in another SUO-CTC sanctioned trial. This trial will include 664 patients with sarcomatoid or clear cell RCC patients.
In conclusion, emerging biological data on rare subtypes of RCC is available and should be used to better “tailor” treatment to disease. The above mentioned emerging studies will stratify the treatment groups according to different histologies instead of “lumping” them together.
Presented By: : Sumata K. Pal
Written By: Miki Haifler, MD, M.Sc., Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA