Prostate Cancer Research Areas
Ongoing trials:
Oligometastatic prostate cancer trials:
EMBARK trial - enrolling for high risk PSA recurrence patients to LHRH vs enzalutamide vs. LHRH + enzalutamide
STAMPEDE trial - M1 - ADT vs ADT + RT in oligometastatic disease
HORRAD-M1b (Netherlands) ADT vs ADT + RT in oligometastatic disease
TRoMbone (UK) low volume M1 radical prostatectomy
NCT01751438 (N. America) m1HSPC systemic therpay vs. systemic + local radiation or surgery
CTLA-4, PDL-1 and vaccines have been looked into, without promising results.
Ipilimumab is a MAB that targes CTLA-4. Prechemotherapy phase III CRPC study showed higher PSA response and progression free survival benefit, but no difference in OS. There is severe diarrhea and treatment related deaths reported.
Pemrolizumab is MAB that targes PD-1. A phase II trial combined w/ enzalutamide for post enzalutamide/abiraterone CRPC showed PSA and disease responses. (1)
AR-V7 is a receptor splice variant, has a poor response to enzalutamide and abiraterone and poor prognosis. If this is positive, suggests better response with taxanes than AR inhibitors (2). No approved assay for this yet.
HSD3B1 encodes an enzyme that makes more androgens be produced in PC and are resistant to ADT. Could be a target for multi drug therapy (3, 4)
Sequencing of tumors can give insight into possible targets for a given patient's cancer. PARP inibitors and platinum based chemo could be used to target DNA repair mechanism mutations.
Oligometastatic prostate cancer trials:
EMBARK trial - enrolling for high risk PSA recurrence patients to LHRH vs enzalutamide vs. LHRH + enzalutamide
STAMPEDE trial - M1 - ADT vs ADT + RT in oligometastatic disease
HORRAD-M1b (Netherlands) ADT vs ADT + RT in oligometastatic disease
TRoMbone (UK) low volume M1 radical prostatectomy
NCT01751438 (N. America) m1HSPC systemic therpay vs. systemic + local radiation or surgery
CTLA-4, PDL-1 and vaccines have been looked into, without promising results.
Ipilimumab is a MAB that targes CTLA-4. Prechemotherapy phase III CRPC study showed higher PSA response and progression free survival benefit, but no difference in OS. There is severe diarrhea and treatment related deaths reported.
Pemrolizumab is MAB that targes PD-1. A phase II trial combined w/ enzalutamide for post enzalutamide/abiraterone CRPC showed PSA and disease responses. (1)
AR-V7 is a receptor splice variant, has a poor response to enzalutamide and abiraterone and poor prognosis. If this is positive, suggests better response with taxanes than AR inhibitors (2). No approved assay for this yet.
HSD3B1 encodes an enzyme that makes more androgens be produced in PC and are resistant to ADT. Could be a target for multi drug therapy (3, 4)
Sequencing of tumors can give insight into possible targets for a given patient's cancer. PARP inibitors and platinum based chemo could be used to target DNA repair mechanism mutations.
- Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016;7(33):52810-52817.
- Scher HI, Lu D, Schreiber NA, et al. Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer. JAMA Oncol. 2016;2(11):1441-1449.
- Agarwal N, Hahn AW, Gill DM, Farnham JM, Poole AI, Cannon-Albright L. Independent Validation of Effect of HSD3B1 Genotype on Response to Androgen-Deprivation Therapy in Prostate Cancer. JAMA Oncol. 2017;3(6):856-857.
- Hearn JW, AbuAli G, Reichard CA, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. The Lancet Oncology. 2016;17(10):1435-1444.