ASCO GU 2017: Actionable targets in germ cell tumors

Orlando, Florida USA (UroToday.com) I80% of GCT patient will be cured with platinum based chemotherapy. On the other hand, resistant disease occurs in about 20% of cases of advanced GCT. The unmet needs in this space are to better understand the biology of GCT and incorporate this biology into treatment with novel therapies. The genomic landscape of GCT is changing. Once thought unrelated to advanced GCT, P53 mutation is now believed to be related to platinum resistance. Furthermore, KRAS mutations are important in transition from pre malignant lesions to GCT and in platinum resistance. Sequencing also showed that nonsynonimous mutation were more common in resistant tumors. Amplification in TP53/MDM2 occurs in 7.7% of advanced platinum resistant GCT and is pivotal in acquiring resistance. Several MDM2 inhibitors are under trial. Another important target is MYCN which is mutated in 4.8% of cases.

To date, no successful clinical trials of molecular targeted agents in patients with advanced GCT were reported. This is mainly due to the rareness of the disease and difficulty in appropriately selecting patients for targeted therapy. A trial examining the effect of sunitinib in advance GCT did not show any objective response. Similar results were shown for pazopanib.

In a recent pan-cancer study assessing RNA sequencing data for CD8A and PDL1 expression from multiple TCGA databases, GCT demonstrated very high levels of expression that are seen only with other highly immune recognized cancers such as melanoma. This suggests the potential role of immunotherapy. 73% and 64% of seminomas and non seminomas respectively were found to be PDL1 positive. Furthermore, PD1 and PDL1 were able to predict PFS and OS. There are several ongoing trials for checkpoint blockade in GCT.

Presenter: Aditya Bagrodia, MD, The University of Texas Southwestern Medical Center

Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA

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