Next Generation Sequencing (NGS) in metastatic castration resistant prostate cancer (mCRPC) to identify targets for individualized treatment: Is it feasible in daily routine?

Abstract

194 Background: Systemic of mCRPC consists of various approaches such as docetaxel, abiraterone, enzalutamide, Radium-223 and cabazitaxel. If all treatment options are exhausted, molecular profiling of biopsies from progressive metastases might enable an individualized approach with targeted therapies. It was the purpose of our study to examine (1) the feasibility of NGS in daily routine, (2) the frequency of treatable mutations and (3) the therapeutic outcome. Methods: From 1/2016 to 12/2017, 214 patients with mCRPC were treated; 52 pts progressed after exposure to all approved systemic therapies. All men underwent biopsies of the progressing lesions to perform mutational analysis via NGS using 9 Multiplex PCR amplicons (AR, ATM, BRCA1/2, CTNNB1, DLL3, PIK3CA, PTEN, RAD51C, TP53) which generation was done with a GeneRead DNAseq Custom Panel V2 (Qiagen). Creation of the library was done with the use of GeneRead DNA Library I Core, GeneRead DNA I Amp Kits and NEXTflex-96 DNA Barcode Adapter. Results: Following lesions were biopsied n = 8 (15.4%) liver, N = 4 (7.7%) lung, n = 4 (7.7%) bone, n = 36 (69.2%) lymph node. Sufficient material was received in all cases. 31 (59.7%) demonstrated wild type in all amplicons vorhanden, n = 21 (40.3%) demonstrated at least 1 potentially treatable mutation: BRCA1/2 or ATM n = 11, AR n = 7, DLL3 n = 3, p53 n = 9, Rad51C n = 4, CTNNB1 n = 4, PTEN/PIK3CA n = 4. Results were discussed in our molecular and clincical phase-I tumor board. Median overall survival oft he pateint cohort is 18.5 (6-34) months. Conclusions: NGS analysis of biopsy samples from progressing metastatic sites is feasible in mCRPC presuming an interdisciplinary setting in the diagnostic and therapy decision making process. NGS results in the identification of treatable mutations in more than one third of patients.