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

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.