Cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 235-235 ◽  
Author(s):  
Fatima Karzai ◽  
Ravi Amrit Madan ◽  
Marc Robert Theoret ◽  
Philip M. Arlen ◽  
Nancy Ann Dawson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acquired Resistance ◽  
Maximum Tolerated Dose ◽  
Cross Resistance ◽  
Published Data ◽  
Phase 2 ◽  
Tumor Resistance ◽  
Castrate Resistant Prostate Cancer ◽  
Previously Treated ◽  
Castrate Resistant

235 Background: Docetaxel (D) improves overall survival in metastatic castrate-resistant prostate cancer (mCRPC), but benefits remain short-lived. Clinical data suggests patients (pts) with mCRPC treated with anti-androgen therapy like abiraterone (AA) or enzalutamide (ENZA) have decreased responses to subsequent therapy due to cross-resistance in the androgen pathway targeted by D, AA, or ENZA(van Soest et al, Eur J Cancer 49:18, 2013). Combining D with other agents, like cabozantinib (C), could target different cellular signaling pathways potentially minimizing tumor resistance. Methods: D naive pts receive 75 mg/m2 IV on day 1 of a 21 day cycle, and prednisone (P) 5 mg po q12 hours with C at 3 dose levels: 20, 40, or 60 mg po daily until maximum tolerated dose (MTD) is defined. In phase 2, pts who have progressed on AA or ENZA, enroll on a randomized 2 arm cohort comparing D plus C to D alone. Results: 20 pts have been accrued; 4 at 20 mg C, 8 at 40 mg C, and 7 at 60 mg C. On phase 2, 1 pt is randomized to D alone. Median age is 68 (44-84 yrs). Median baseline PSA is 94.7 (0.01-754.1 ng/mL). Gleason score is 9 (7-10). Median cycles is 9.5 (1-33). 8 pts have bone only disease, 12 pts have bone and soft tissue disease. Common grade 2 and grade 3 adverse events possibly related to C: hand/foot syndrome (4/16), oral mucositis (4/16), hypophosphatemia (4/16), and fatigue (3/16). The MTD of C is 40 mg daily with D. 15 pts were previously treated with AA or ENZA. In 13 patients previously treated with AA, median PFS has not been reached, with a median potential follow up of 12.4 months. Six month PFS is 77.8% and 9 month PFS is 60.5%. Conclusions: D plus P may have limited benefits after disease progression on AA as seen in 3 retrospective analyses demonstrating a median PFS survival of 4.6 months or less (Mezynski J, et al. Ann Oncol 23;11, 2012) (Aggarwal R, et al. Clin Genitourin Cancer 12;5, 2014) (Schweizer MT, et al. Eur Urol 66;4, 2014). PFS results seen in this trial compare favorably to previously published data of treatment with D after AA in mCRPC, suggesting the addition of C to D may help overcome acquired resistance. Further randomized trials will determine if C in combination with D will enhance clinical outcomes. Clinical trial information: NCT01683994.

scholarly journals LBA-25 RESIST-PC PHASE 2 TRIAL: 177LU-PSMA-617 RADIONUCLIDE THERAPY FOR METASTATIC CASTRATE-RESISTANT PROSTATE CANCER

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Jeremie Calais* ◽  
Wolfgang Fendler ◽  
Matthias Eiber ◽  
Michael Lassmann ◽  
Magnus Dahlbom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radionuclide Therapy ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals Glucocorticoid Receptor is distinct from Androgen Receptor function in Castrate-Resistant Prostate Cancer

2020 ◽  
Author(s):  
Dalal El-Barbarawi ◽  
Tiha M Long
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Gene Expression Analysis ◽  
Target Gene ◽  
Invasive Disease ◽  
Published Data ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Commonly used therapies for prostate cancer (PC) that block androgen receptor (AR) signaling inhibit regrowth, but aggressive castrate-resistant (CR)PC abrogates anti-androgen therapy. Recently published data shows that glucocorticoid receptor (GR) can drive the growth of CRPC when AR is blocked, by mimicking AR activity. Due to the evolution of CRPC into a more invasive disease, we hypothesized that GR-driven CRPC has different activities than AR that promote progression to metastatic disease. To test this hypothesis, we performed gene expression analysis on available datasets to determine which pathways correlate with GR target gene expression. Furthermore, we investigated gene expression in CWR-22Rv1 CRPC cells via qRT-PCR. Our results show that GR-activation in AR-blocked cells induces different genes than AR, suggesting that GR-driven CRPC is unique from AR-driven disease. The scientific contribution of our research may reveal new mechanisms by which GR drives PC progression and unveil novel therapeutic targets.

Review of the real-world prevalence of mHSPC, nmCRPC, mCRPC, and gene alterations associated with HRR in prostate cancer (PC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 229-229
Author(s):  
Neal D. Shore ◽  
Louisa Oliver ◽  
Irene Shui ◽  
Alicia Gayle ◽  
On Yee Wong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
English Language ◽  
Treatment Guidelines ◽  
Grey Literature ◽  
Phase Iii ◽  
Published Data ◽  
Global Epidemiology ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Gene Alterations

229 Background: The clinical journey of PC is evolving rapidly. New hormonal agents (NHA) have demonstrated clinical efficacy in metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC) and metastatic castrate-resistant prostate cancer (mCRPC). A shift in the treatment landscape considering precision medicine, recently supported by the phase III PROFOUND study, suggests updates to the currently limited clinical guideline recommendations for genomic testing. Better understanding of the patient pathway and respective proportion of patients to support patient care is needed. The objective of this SLR was to summarize published literature on the prevalence of mHSPC, nmCRPC, mCRPC and HRR gene alterations. Methods: An SLR was conducted across nine databases in OVID to capture English language studies published 01/2009–05/2019 on global epidemiology and clinical practice trends for mHSPC, nmCRPC, mCRPC and HRRm. 4,732 papers were identified which were systematically screened for inclusion. Grey literature searches included 10 conference proceedings from 2014–2019. Results: In total, 244 observational publications met the inclusion criteria - 4 studies reported the prevalence of mCRPC, 3 on nmCRPC and 0 on mHSPC. From these, the estimated prevalence of mCRPC and nmCRPC is 1.6–2.1 and 1.1–2.1 per 100 PC cases, respectively. HRRm were investigated in 13 publications with next generation sequencing of tissue and blood samples being reported as the most frequent method. Of the HRR gene alterations examined, BRCA2 were found to have the highest prevalence with a range of 4.5–9.3 and 1.1–15.1 per 100 overall PC cases for germline and somatic gene alterations, respectively. Other prevalent HRR gene alterations included germline ATM, BRCA1 and CHEK2. Conclusions: Limited data are available evaluating the prevalence of mHSPC, nmCRPC and mCRPC required to quantify the burden of these populations suggesting a lag in the published literature following updates to US treatment guidelines. Our review also shows that HRR gene alterations, specifically BRCA2, are prevalent in PC consistent with recently published data on PROFOUND population.

Application of a novel method weighing drug costs against survival in castrate-resistant prostate cancer cancer.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 271-271
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Prostate Cancer ◽  
Drug Costs ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Castrate Resistant Prostate Cancer ◽  
Previously Treated ◽  
Novel Method ◽  
Different Populations ◽  
Initial Survey ◽  
Castrate Resistant

271 Background: In the last few years, 5 new anticancer drugs have been introduced for the treatment of castration-resistant prostate cancer (CRPC). The objective was to apply a simplified methodology of weighing drug costs against overall survival (OS) in CRPC. Methods: Estimated cost in United Sates (US) dollars of an entire treatment course of an evaluated drug was divided by previously reported median OS gain over control. An initial survey of 45 drugs demonstrated that the maximal cost/OS/day gain was $757. Accordingly, a scale of crude scores was constructed with a 0% assigned to a cost/OS gain greater than $1,000 and 100% to a cost/OS gain of $1. Value scores were calculated after adjusting for quality of life (QoL), adverse events (AEs), and specialized administration and preparation (AP). Results: The lowest cost/OS gain and highest value score were demonstrated by generic docetaxel. Enzalutamide in previously-treated and abiraterone in chemo-naïve and treated patients x 6 months showed cost/OS gain lower than that of docetaxel but significantly higher than cabazitaxel. Pricing of sipuleucel-T based on cost of the entire course partly accounted for its highest cost/OS and lowest scores. Extending abiraterone and enzalutamide treatment to 12 months increased cost/OS gain and decreased scores. Conclusions: Methodology was proposed to weigh drug cost against OS/day gain with and without adjustment for QoL, AEs, and AP. Results in CRPC tend to support use of docetaxel, abiraterone, and enzalutamide rather than cabazitaxel and sipuleucel-T. Varying drug indications and different populations within the CRPC spectrum preclude direct drug comparison.

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