#AUA14 - Anti-PD1 agents in kidney cancer - Session Highlights

ORLANDO, FL USA (UroToday.com) - Dr. David McDermott presented an overview of anti-PD-1 agents in kidney cancer. Nivolumab (anti PD-L1 agent) showed efficacy in a phase I trial for patients with metastatic RCC (n=34). There was a 29% objective response rate with a median progression-free survival time of 7.3 months. The drug was well tolerated with minimal severe adverse events, and remarkably, treatment-free survival was achieved in a few patients. Dr. McDermott highlighted a few main questions of immediate pertinence to PD-1 therapy: Is clinical benefit a reflection of patient selection? How many responses will be durable off therapy? How do we identify responders pre treatment? And can PD-L1 expression alone on tumor reliably predict responders?

auaWith regards to the observed clinical benefit, Dr. McDermott stressed that the phase 1 trial results most certainly reflect selection bias. Regarding use of PD-L1 biomarkers to predict treatment response, the answer to this question is more ambiguous. In a small study of only 5 patients, PDL1 expression in pre-treatment tumor biopsies correlated with response to therapy and outcomes. In a separate study, if tumor tissue was PDL1+, response rates to therapy were 20% versus 10% for PDL- tumors. Heterogeneous PDL1 expression in the primary tumor or between primary and metastases can lead to false negative results when PDL1 is evaluated in a single portion of the nephrectomy specimen.

The potential impact of discordant PD-L1 expression was further evaluated among 34 primary/met pairs following surgical excision. Ten (29%) were PD-L1 positive in primary tumor, while 7/10 were PDL1 positive in met. Primary PD-L1 staining is very heterogeneous, whereas metastatic PD-L1 staining is more homogeneous. Dr. McDermott then closed by previewing the phase 2 nivolumab data for RCC, which revealed a 20% objective response rate with a median OS of 25 months. Combining nivolumab with VEGF TKI or ipilimumab yielded objective response rates of 40-50%. ECOG 1813 is an ongoing phase 2 trial of neoadjuvant versus adjuvant PD-1 blockade in non-metastatic RCC. Clearly this is an exciting area of research for RCC treatment.

Presented by David F. McDermott, MD at the American Urological Association (AUA) Annual Meeting - May 16 - 21, 2014 - Orlando, Florida USA

Beth Israel Deaconess Medical Center, Boston, MA USA

Written by Jeffrey J. Tomaszewski, MD, medical writer for UroToday.com



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