ASCO GU 2021: Comprehensive Genomic Profiling in Patients with Relapsed/Refractory Germ Cell Tumors

(UroToday.com) Though clinical outcomes for advanced germ cell tumors have been significantly improved with the utilization of cisplatin-based chemotherapy regimens, approximately 400 patients a year die from relapsed or refractory germ cell tumors. To further explore the genetic properties of cisplatin refractory or relapsed germ cell tumors, 52 tumors from a single institution were profiled using a hybrid-capture commercial assay and also analyzed for PD-L1 expression using the DAKO 22C3 immunohistochemistry antibody.


Patients included in the study all had received first-line cisplatin-based chemotherapy. The median age at diagnosis was 33, and 85% of patients had a primary testicular tumor. Of the 52 patients, 46 were non-seminoma, and 23% of patients were platinum-refractory. Most tumors that were sequenced were from a non-primary tumor metastatic site.

The median tumor mutational burden in this cohort was 3.5 mutations per megabase. Four patients had a TMB greater than 10, and 2 patients had a TMB greater than 20. Of the 48 patients evaluated for microsatellite instability, 1 patient was positive. Three patients had PD-L1 expression greater than 50%, and 10 of 17 total patients analyzed had PD-L1 expression greater than 1%.

The genomic alterations detected are shown below. In seminomas, the most common alterations were mutations in KIT, TET2, BRD4, and NRAS as well as copy number alterations in KRAS, CCND2, and FGF23. The most common alterations in non-seminoma were copy number changes in FGF6, FGF23, KDM5A, and KRAS as well as mutations in TP53 and APC.

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Presented by: Reem Akel, MD, Indiana University School of Medicine

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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