Abstract
528 Background: Advances in comprehensive tumor molecular pathology in genito-urinary (GU) tumors have driven development of targeted agents since ten years and changed the landscape of GU tumors treatment. We describe our experience with the institutional molecular trial ProfiLER. Methods: Retrospective review of patients with advanced genitourinary malignancies included in the prospective molecular profiling trial ProfiLER (NCT01774409) Tumor samples were analyzed by sequencing a 69 gene panel by next generation sequencing (NGS, Ion torrent PGM system) and whole genome array comparative genomic hybridization (Agilent platform). Clinical data were collected retrospectively. Cases were presented in a molecular board to drive prescription of molecular targeted therapy (MTT) according to the molecular abnormalities observed. Results: Between February 2013 and December 2018 156 adult patients were included, 42 had kidney cancer (including 32 clear cell carcinoma, 5 papillary type 2); 38 prostate cancer, 52 urothelial carcinoma including (16 upper tract), 12 cisplatin-refractory testicular germ cell tumor, 4 penile cancer, 3 adenocarcinoma of the urachus, 2 urethral carcinoma and 3 Leydig cell tumor. Median age at inclusion was 62 years (range 19, 80). Overall NGS and CGH failed in 11.5% of cases, and in 24% of prostate cancer cases.28.8% patients had at least one actionable target (n=45) with a recommended MTT. Only 17.8 % (n=8) patients actually received MTT corresponding to 5.1% of the total screened population. Only one patient had a clinical benefit from MTT. The most frequently initiated MTT were PIK3/AKT/mTOR pathway inhibitors (44,4%), FGRF/EGFR pathway inhibitors (13.3%) PARP inhibitors (8.7%) or cyclin kinase inhibitors (8.7%). The most frequent reasons for lack of MTT initiation were early death, ineligibility for clinical trials due to general condition. Conclusions: Non tumor-specific molecular profiling is feasible in GU cancers. However the use of targeted sequencing with a tumor type specific panel and at an earlier clinical stage may improve the proportion of MTT recommendations.
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