In this study, the authors performed complete genomic profiling (CGP) on a series of 44 patients with PMNSGCT and compared the results with chemorefractory, metastatic pure seminomatous (Sem) and non-seminomatous (NS) testicular GCT.
Archival tissues from 44 chemotherapy-treated and refractory PMNSGCT, 22 Sem and 86 NS were sequenced by an FDA-approved hybrid-capture based CGP (FoundationONE) at a CLIA-certified laboratory. Microsatellite instability (MSI) was determined on 114 loci and tumor mutational burden (TMB, reported as mutations [mut]/Mb) was determined on 1.1 Mbp of sequenced DNA.
The PMNSGCT patients, of whom there were 43 males and 1 female, had a median age (similar median to the NSGCT patients, but which was significantly younger than the Sem pts (P = 0.007). Yolk sac differentiation was most frequent in PMNSGCT (39%).
The mean genomic alterations (GA) per tumor was similar in all 3 GCT subtypes. Notable differences in GA in PMNSGCT vs NS included significantly higher TP53 pathway GA (81.6% vs 19.8%; p < 0.0001) and PIK3CA pathway GA (43.1% vs 6.9%; P < 0.0001) and lower cell-cycle pathway GA (22.7% vs 55.8%; P = 0.0004) [Table]. PMGCT featured more frequent targetable GA in BRAF (7%), ERBB2 and NTRK1-3 (2% both) than PS or NS. KRAS GA frequencies were similar in all the 3 groups. There were no MSI-H PMNSGCT cases.
The mean TMB in PMNSGCT was similar to the Sem and NS tumors, but there were more TMB ≥10 and ≥20 mut/Mb in the PMNSGCT group.
A summary of these findings is seen below:
The authors concluded that the array of genomic alterations in PMNSGCT were similar to those from testicular NS, with a higher frequency of yolk sac differentiation, TP53 GA and slightly increased opportunities for targeted therapies (BRAF, ERBB2 and NTRK1) and immunotherapies (4.5% with TMB ≥20 mut/Mb). F
Presented by: Andrea Necchi, MD, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, twitter: @tchandra_uromd, @TjuUrology at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23, 2018, Munich Germany