Abstract 1095
Background
Tumor profiling by tNGS is increasingly common in patients (pts) with metastatic solid tumors. It is unclear if this strategy leads to changes in treatment decision for mPCa pts.
Methods
A retrospective analysis of mPCa pts treated at Cleveland Clinic with available comprehensive genomic profiling using tumor tissue (FoundationOne, F1) or cell-free circulating tumor DNA (FoundationAct, Guardant360) was conducted. Targetable genomic alterations (tGA) were defined as a change in the copy number (amplification/duplication) or a mutation (deletion/rearrangement/truncation/fusion) in AR, DNA repair genes, mismatch repair (MMR) genes, cyclin-dependent kinases (CDK), ERBB2, BRAF, TSC and PIK3-mTOR pathway.
Results
Within 2013-2017, 66 pts, median age 68y (49-85), median ECOG PS1 (0-2), with mPCa, Gleason 9 (6-10), 86% castration-resistant (CRPC), received a median of 3 (0-7) systemic treatments for CRPC before tNGS panel. The most common tNGS platform used was F1 (91%) based on archival tumor tissue (45% primary, 55% metastatic). Overall, frequent alterations included TP53 (42%), PTEN (35%), AR (30%), DNA repair (30%), PIK3CA signaling pathway (21%), CDK (15%) and MSI-H/MMR (9%). Median tumor mutational burden was 7 (0.8-32) mutations/Mb. Among 45 with tGA+ pts, tNGS influenced treatment in 13 pts: PARP inhibitor (n = 7; olaparib 6, niraparib 1), mTOR inhibitor (n = 4; everolimus 3, temsirolimus 1), pembrolizumab 2, trastuzumab 1. PSA decline was observed in 54% and median (m) PFS was 4.1 months (95%CI, 2.8-5.4) with 9 pts (69%) progressing on therapy to date. Among tGA+ pts not treated with tGA-based therapy, first subsequent treatment (n = 17) included chemotherapy (71%), abiraterone (18%), cabozantinb (6%) and other (6%). PSA decline was observed in 24% and mPFS was 4.3 months (95%CI, 2.6-6.0); 12 pts (71%) progressed on therapy. There was no difference in mPFS between tGA+/tGA- pts (p = 0.652). The median OS was 60.4 months (95%CI, 51.9-68.9) compared with 17 months (95%CI, 10.5-23.5) after tNGS was ordered.
Conclusions
tNGS was ordered somewhat late in the course of the disease. tGA results only impacted therapy selection in 20% of pts but with modest clinic benefit.
Clinical trial identification
Legal entity responsible for the study
Taussig Cancer Institute Cleveland Clinic.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
P. Grivas: Consultant, advisor: Foundation Medicine, Genentech, Dendreon, Bayer, Exelexis, Merck, Bristol-Myers Squibb, AstraZeneca, Biocept, Clovis Oncology, EMD Serono, Seattle Genetics; Research funding: Mirati Therapeutics, Genentech/Roche, Merck, Oncogenex, Bayer, Pfizer, AstraZeneca. B.I. Rini: Consultant, advisor: Corvus Pharmaceuticals, Merck, Pfizer; Research funding: Bristol-Myers Squibb (Inst), Merck (Inst), Pfizer (Inst), Roche/Genentech (Inst); Funding travel, accommodations and expenses: Pfizer. D. Sohal: Consultant, advisor: Perthera, Foundation Medicine; Research funding: Novartis, Celgene, OncoMed, Bayer, Genentech/Roche. J.A. Garcia: Consultant, advisor: Sanofi, Pfizer, Bayer, Eisai, Exelexis, Medivation/Astellas, Genentech/Roche; Research funding: Pfizer, Astellas Pharma, Orion Pharma GmbH, Bayer, Janssen Oncology, Genentech/Roche, Lilly. All other authors have declared no conflicts of interest.