External Validation of a Prognostic Model Predicting Overall Survival in Metastatic Castrate-resistant Prostate Cancer Patients Treated with Abiraterone

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).

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Addition of carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in post-second generation hormone therapy setting: Does it improve treatment response and survival outcomes?

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17540 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17540-e17540

Author(s):

Jamal Alamiri ◽

Mohamed E. Ahmed ◽

Jack R. Andrews ◽

Manaf Alom ◽

Giovanni Motterle ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Hormone Therapy ◽

Disease Progression ◽

P Value ◽

Versus Group ◽

Group A ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Group B

e17540 Background: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after treatment with 2nd generation hormone therapy (2nd-HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing 2nd-HT. We sought to evaluate three common chemotherapy regimens in this setting. Methods: We retrospectively identified 150 patients with mCRPC with disease progression on enzalutamide or abiraterone. 92 patients were chemo-naïve, while 58 patients had previously received docetaxel chemotherapy prior to 2nd-HT. After failing 2nd-HT, 90 patients received docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). Favorable response was defined by ≥50% reduction in PSA level from baseline after a complete course of chemotherapy. Survival outcome was assessed for 30-month overall survival. Results: Mean (SD) age was 71.2 (8.28), 69.5(8.38) and 67.2 (8.36) for group (A), (B) and (C), respectively. Mean (SD) pre-chemotherapy PSA was 63.8 (138.18), 58.5 (118.15) and 53.7 (88.15) for group (A), (B) and (C), respectively. Mean (SD) Gleason score was 7.9 (1.1), 8.4 (0.88) and 8.1 (1.06) for group (A), (B) and (C), respectively. Patients in group (B) were 2.6 times more likely to have a favorable response compared to group (A) (OR = 2.625, 95%CI: 1.15 - 5.99) and almost 3 times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04 – 8.54) (p-value = 0.0442). We report a Hazard Ratio (HR) of 3.1 (95% CI 1.31-7.35; p = 0.0037) between patients in group (A) versus group (B), and a HR of 4.18 (95% CI 1.58-11.06; p = 0.0037) between patients in group (C) versus group (B). Thirty-month overall survival was 70.7%, 38.9%, and 30.3% for group (B), (A), and (C) respectively (p-value = 0.008). Conclusions: Our data demonstrate improved response and cancer-specific survival in patients with treatment-refractory mCRPC on docetaxel plus carboplatin compared to docetaxel or cabazitaxel alone. Selection bias is inherent in any retrospective study; however, our finding suggests that clinicians may consider docetaxel plus carboplatin in mCRPC patients who fail 2nd-HT. Further prospective studies are warranted.

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Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.228 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 228-228

Author(s):

Niamh Peters ◽

John Gaffney ◽

Emma Connolly ◽

Richard Bambury ◽

Derek Gerard Power ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Alkaline Phosphatase ◽

Real World ◽

Median Number ◽

Prior Chemotherapy ◽

Factors Associated ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

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PCN116 Mapping FACT-P to EQ-5D in a Large Cross-Sectional Study of Metastatic Castrate-Resistant Prostate Cancer Patients

Value in Health ◽

10.1016/j.jval.2012.08.2156 ◽

2012 ◽

Vol 15 (7) ◽

pp. A430 ◽

Cited By ~ 2

Author(s):

J. Diels ◽

M. Spencer ◽

P. Hamberg ◽

P. Wheatley Price ◽

R.N. Dass

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

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Detection of AR-V7 in Liquid Biopsies of Castrate Resistant Prostate Cancer Patients: A Comparison of AR-V7 Analysis in Circulating Tumor Cells, Circulating Tumor RNA and Exosomes

Cells ◽

10.3390/cells8070688 ◽

2019 ◽

Vol 8 (7) ◽

pp. 688 ◽

Cited By ~ 8

Author(s):

Mohammed Nimir ◽

Yafeng Ma ◽

Sarah A. Jeffreys ◽

Thomas Opperman ◽

Francis Young ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Digital Pcr ◽

Liquid Biopsies ◽

Tumor Biopsy ◽

Highly Sensitive ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood samples from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 samples and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome samples. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC samples should be considered the liquid biopsy of choice for the detection of this clinically important biomarker.

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