ASCO 2017: Inter and intra-tumor heterogeneity of PD-L1 and MET expression in metastatic renal cell carcinoma

Chicago, IL ( Although inhibition of PD-1/PD-L1 and MET receptors have clinical efficacy in metastatic renal cell carcinoma (mRCC), their expression is not a good enough predictive biomarker. One possible explanation might be the heterogeneity between the sites of disease. Dr. Derosa, presented a study aiming to evaluate PD-L1 and cMET expression in primary and metastatic sites (brain (BM)/pancreas (PM)) RCC lesions and their correlation with clinicopathologic characteristics. 

For the purpose of this trial, RCC specimen from 5 different French institutions were collected between November 2015 and October 2016. Clinicopathologic characteristics were assessed by revision of samples. PD-L1 >1% and cMET>=50% expression in tumor cells (TC) and immune cells (IC) were assessed by immunohistochemistry. 

The results demonstrated 181 resected RCC specimens that were successful collected (43 primary tumors and 138 metastases (87 BM/51 PM)).  Overall, 22%, 51% and 23% of patients had at least one specimen expressing PD-L1 TC, IC and cMET, respectively. In primary tumours, the proportion was 12%, 50% and 0%, respectively. In metastasis, the proportion of PD-L1 TC was 22% (23% in BM vs 19% in PM, p = 0.631), PD-L1 IC was 48% (47% in BM vs 49% in PM, p = 0.821) and cMET was 24% (35% in BM vs 2% in PM, p < 0.001). Comparing paired samples (primary tumour and metastasis) there was discordances of PD-L1 in TC or IC and of MET expression in 30%, 27% and 24% of samples, respectively. The discordance in PD-L1 TC or IC and cMET between primary tumor and PM/BM was 15%/40%, 33%/22% and 0%/67%, respectively. 

In summary, this large analysis demonstrated heterogeneity between primary tumor and metastases (brain/pancreatic lesions) in mRCC, PD-L1 and cMET expression. This suggests that metastatic lesions should be assessed for these markers as well, as possible predictive biomarkers.

Presented By: Lisa Derosa, Department of Cancer Medicine, Gustave Roussy Cancer Campus, Paris-Sud University, Villejuif, France

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA