Pembrolizumab and olaparib in a cisplatin-refractory testicular cancer patient with a high TMB: first case report

van Creij, Nils C. H. and Klinglmair, Gerald and Gruber, Leonhard and Partl, Antonia and Zeimet, Alain G. and Santer, Frederic R. and Schnaiter, Simon and Mayr, Roman and Lackner, Felizian and Culig, Zoran and Seeber, Andreas and Pichler, Renate (2025) Pembrolizumab and olaparib in a cisplatin-refractory testicular cancer patient with a high TMB: first case report. THERAPEUTIC ADVANCES IN UROLOGY, 17: 1756287225. ISSN 1756-2872, 1756-2880

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Abstract

Germ cell tumors (GCTs) represent about 5% of urological cancers affecting mostly younger males with increasing incidence in the last decades. GCTs are very sensitive to cisplatin-based therapy and are highly curable regardless of metastatic stage, likely based on having inherited unique mechanisms of sensitivity to DNA damage and other stressors to prevent germline mutations. Here, we present the first case of a 60-year Caucasian male with a heavily pretreated, cisplatin-refractory extragonadal non-seminomatous GCT (choriocarcinoma) treated with pembrolizumab and olaparib based on high programmed death-ligand 1 expression (tumor proportion score 50% and a combined positive score 55%) high tumor mutational burden, borderline genomic loss of heterozygosity, and a heterozygous variant of uncertain significance in the DNA repair gene ATM, as confirmed by next-generation sequencing (NGS) analysis. Despite a notable decrease in b-hCG within 4 weeks after starting pembrolizumab and olaparib, b-hCG increased steadily again afterward. In addition, the patient developed an immune-related pneumonitis with a fatal outcome 3 months later. NGS with subsequent targeted treatment possibilities might present a helpful step toward precision medicine in GCT patients who have exhausted all other conventional treatment options, and genetic testing should therefore be offered to patients prior to progression.

Item Type: Article
Uncontrolled Keywords: GERM-CELL TUMORS; PD-L1 EXPRESSION; case report; germ cell tumors; immunotherapy; PARPi
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 May 2026 12:18
Last Modified: 26 May 2026 12:18
URI: https://pred.uni-regensburg.de/id/eprint/67401

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