scholarly journals Exploring Spatial-Temporal Changes in 18F-Sodium Fluoride PET/CT and Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

2020 ◽  
Vol 38 (31) ◽  
pp. 3662-3671
Author(s):  
Christos E. Kyriakopoulos ◽  
Elisabeth I. Heath ◽  
Anna Ferrari ◽  
Jamie M. Sperger ◽  
Anupama Singh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
Bone Lesion ◽  
Specific Antigen ◽  
Standardized Uptake Value ◽  
Ct Scans ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pet Ct ◽  
Psa Progression

PURPOSE Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression. PATIENTS AND METHODS Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382 ). 18F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI. RESULTS Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUVhetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUVtotal) was seen at the time of progression, as measured by 18F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI. CONCLUSION We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.

scholarly journals Exploratory Study of [18F]fluciclovine PET/CT for Response Assessment to Docetaxel in Patients with Metastatic Castration Resistant Prostate Cancer

2020 ◽  
Author(s):  
Akinyemi A Akintayo ◽  
Mehmet A Bilen ◽  
Olayinka A Abiodun-Ojo ◽  
Omer Kucuk ◽  
Bradley Carthon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Scan ◽  
Progressive Disease ◽  
Specific Antigen ◽  
Response Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pet Ct ◽  
Psa Response ◽  
Psa Progression

Abstract Background The ability to accurately monitor response to treatment in patients with metastatic castration resistant prostate cancer (mCRPC) on chemotherapy has been a challenge. Conventional methods of therapy response assessment have limitations and molecular imaging has been explored as an important alternative. We set out t o determine if anti-1-amino-3-anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/computed tomography (PET/CT) changes reflect response to docetaxel chemotherapy in mCRPC. Results Seven patients with mCRPC were enrolled. Each patient was scheduled to have [18F]fluciclovine PET/CT at baseline, and after 1 and 6 cycles of chemotherapy. Uptake parameters were recorded in the prostate/bed and up to 10 metastatic lesions. Decrease in uptake of ≥30% was considered response (R); appearance of new lesions or >30% increase in uptake was progressive disease (PD); and change of < 30% uptake was stable disease (SD). Prostate specific antigen (PSA) was obtained at baseline and before each cycle. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Assessment of response was based on Prostate Cancer Clinical Trial Working Group 3 recommendations. Correlation between [18F]fluciclovine uptake and time to PSA progression was also determined. All patients completed the 1 st and 2 nd [18F]fluciclovine PET/CT, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients and 3/4 (75%) patients after 1 and 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. Mean SUVmax and SUVmean were significantly higher in patients with progressive disease versus non-progressive disease after 6 cycles of docetaxel (p<0.05), but not at baseline or after 1 cycle of docetaxel. There was non-significant correlation of changes in [18F]fluciclovine uptake with changes in PSA after 1 and 6 cycles of docetaxel. There was no significant correlation between PET parameters and time to PSA progression. Conclusion [18F]fluciclovine PET/CT has better correlation than CT or bone scan with PSA response for patients with mCRPC treated with docetaxel. [18F]fluciclovine PET/CT did not predict time to PSA progression. Larger studies exploring the utility of [18F]fluciclovine PET for response assessment are recommended.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Comparison of enzalutamide and bicalutamide in patients with non-metastatic castration-resistant prostate cancer: Number needed to treat to achieve one additional patient free of clinical progression events.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 228-228
Author(s):  
Lawrence Ivan Karsh ◽  
David F. Penson ◽  
Raoul Concepcion ◽  
Scott Flanders ◽  
Bruce A. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Absolute Risk ◽  
Specific Antigen ◽  
Additional Patient ◽  
Number Needed To Treat ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Free Psa ◽  
Castration Resistant ◽  
Psa Progression

228 Background: Androgen receptor inhibitors enzalutamide (ENZA) and bicalutamide (BIC) are used to treat metastatic castration-resistant prostate cancer (mCRPC). The Phase 2 STRIVE trial included 35% non-metastatic (m0) and 65% metastatic CRPC patients (pts); ENZA reduced the risk of progression or death among pts, with an adverse event profile consistent with previous trials. The objective of this analysis was to compare ENZA with BIC using the number needed to treat (NNT) to achieve one additional pt with m0CRPC, with either a progression-free survival (PFS) event, radiographic PFS (rPFS), or free of prostate-specific antigen (PSA) progression at 1 year and 2 years. Methods: The 1- and 2-year event rates of PFS, rPFS, and progression-free PSA among pts treated with ENZA and BIC were obtained from the STRIVE trial report. The NNT was calculated as the reciprocal of the absolute risk reduction between ENZA and BIC at each time point. This represents the number of pts that need to be treated with ENZA, compared with BIC, to obtain one additional pt free of a clinical progression event. PFS was defined as the time from randomization to investigator-assessed radiographic (bone or soft tissue) progression, PSA progression, or death. The 95% confidence interval (CI) of the NNT was derived based on the 95% CI of the event rate difference. Results: The NNT to achieve one additional pt with PFS at 1 year, comparing ENZA with BIC, was 2.2 (95% CI 1.7, 3.4), suggesting that treating three pts with ENZA instead of BIC would result in one additional pt free of progression or death at the end of 1 year. The NNT to achieve one additional pt with PFS at 2 years was also 2.2 (95% CI 1.5, 3.7). For rPFS, the NNTs comparing ENZA with BIC were 4.7 (95% CI 2.8, 14.6) and 3.0 (95% CI 2.0, 6.1) at 1 and 2 years, respectively. For progression-free PSA, the NNTs were 2.0 (95% CI 1.5, 2.8) and 2.0 (95% CI 1.4, 3.3) at 1 and 2 years, respectively. Conclusions: This analysis supports the superior clinical benefit of ENZA versus BIC in men with m0CRPC. Pts treated with ENZA showed low NNT values across all clinical outcomes and time points. Clinical trial information: NCT01664923.

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

A phase II study of onvansertib (PCM-075) in combination with abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS336-TPS336
Author(s):  
David Johnson Einstein ◽  
Atish Dipankar Choudhury ◽  
Philip James Saylor ◽  
Lillian Werner ◽  
Mark G. Erlander ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Control ◽  
Phase 1 ◽  
Specific Antigen ◽  
Specific Inhibitor ◽  
Circulating Tumor Dna ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression ◽  
Hormonal Therapies

TPS336 Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a leading cause of cancer-related deaths worldwide. Although abiraterone (abi) in either the castration-sensitive or castration-resistant setting increases survival, resistance is universal and limits the efficacy of subsequent hormonal therapies. Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase that regulates mitotic functions and promotes the progression of cells through mitosis, and it is highly upregulated in prostate cancer following castration. PLK1 inhibition enhances the efficacy of abi in cell line models as well as patient-derived tumor xenografts via several mechanisms. Onvansertib (PCM-075; Trovagene, Inc.) is the first orally available PLK1-specific inhibitor. In phase 1 testing, onvansertib demonstrated a manageable safety profile, with transient hematologic effects as its most prominent, yet reversible, toxicity. Methods: The goal of this phase 2 study (NCT03414034) is to observe the effects of onvansertib in combination with abi + prednisone on disease control, as assessed by prostate-specific antigen (PSA) decline or stabilization after 12 weeks of study treatment, in subjects with mCRPC and early resistance to abi. Patients will be enrolled at time of PSA progression while on standard abi. A completed 3-patient safety lead-in phase tested the safety of the combination of onvansertib with abi, and the accruing expansion phase will treat 29 more patients with onvansertib (24 mg/m2 orally on days 1-5 of a 21-day cycle) plus abi (administered orally and continuously once daily with prednisone) until time of radiographic or symptomatic progression. With 32 patients, there will be 90% power to detect a change in disease-control rate from 10% (null) to 30% (alternative). Based on a Simon’s two-stage optimal design, the study will terminate early if < 2 of the first 13 patients achieve disease control. Exploratory analyses include evaluations of predictive genomic biomarkers in circulating tumor cells and circulating tumor DNA, including alterations of oncogenes and tumor suppressors implicated in PLK1 sensitivity within preclinical models. Clinical trial information: NCT03414034.

scholarly journals Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel

2018 ◽  
Vol 12 (8) ◽  
Author(s):  
Daniel W. Yokom ◽  
John Stewart ◽  
Nimira S. Alimohamed ◽  
Eric Winquist ◽  
Scott Barry ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
Proportional Hazards ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Factors ◽  
Castration Resistant

Introduction: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel.Methods: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response.Results: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression.Conclusions: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.

Antitumor activity of abiraterone, enzalutamide, and docetaxel following treatment with diethystilbestrol in castration-resistant prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e581-e581
Author(s):  
Sandra Assoun ◽  
Luca Campedel ◽  
Morgan Roupret ◽  
Christophe Vaessen ◽  
Jerome Parra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Median Time ◽  
Specific Antigen ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Clinicopathologic Characteristics ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

e581 Background: Docetaxel and Next-Generation Anti-Androgens (NGAA) including abiraterone and enzalutamide represent the standard of treatment for patients with castration-resistant prostate cancer (CRPC). Treatment sequencing of these agents is a challenge. Recent studies identified cross-resistances between hormonal therapies and taxanes, as well as between different NGAA. In aiming to elucidate whether synthetic oestrogen diethylstilbestrol (DES) therapy impacts the efficacy of later-line treatments or not, we evaluated the antitumor activity of NGAA and docetaxel following DES therapy in CRPC patients. Methods: All patients with CRPC treated at Pitié-Salpêtrière hospital in first-line setting with DES from September 1995 to July 2016 were retrospectively identified. We evaluated further activities of abiraterone, enzalutamide and docetaxel in those patients after DES therapy, using Prostate Cancer Working Group 3 criteria. Clinicopathologic characteristics, including age, performans status, metastatic sites at diagnosis and treatments initiation, and data survival were also assessed. Results: Twenty-three patients with CRPC were initially treated with DES with a median time to prostate-specific antigen (PSA) progression of 9.7 months (range, 4.7-20.3). Thirteen patients(56.5%) received abiraterone or enzalutamide before docetaxel and 21 patients (91.3%) after. Median age at first NGAA initiation was 79 years) range, 55-91). Only one patient (7.7%) achieved a PSA decline before docetaxel and two out of 18 evaluable patients (11.1%) after docetaxel. Median time to PSA progression and overall survival with a NGAA treatment were respectively 2.8 (range, 2.0-4.1) and 16.5 months(range, 4.3-31.0). Fifty percent of patients showed a PSA response with docetaxel. No clinical factors were found to be significantly associated with PSA response to NGAA treatment, nor to docetaxel. Conclusions: The activity of NGAA appears markedly limited after a DES therapy, regardless of the PSA response to docetaxel. These data suggest the likelihood of a cross-resistance mechanism between DES and NGAA, without no impact on taxanes pathways.

scholarly journals Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate

2010 ◽  
Vol 28 (9) ◽  
pp. 1489-1495 ◽  
Author(s):  
Alison H.M. Reid ◽  
Gerhardt Attard ◽  
Daniel C. Danila ◽  
Nikhil Babu Oommen ◽  
David Olmos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
End Point ◽  
Castration Resistant ◽  
Psa Progression

Purpose The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). Patients and Methods In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of ≥ 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of ≥ 30% and ≥ 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration. Results Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of ≥ 30%, ≥ 50% and ≥ 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study ≥ 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a ≥ 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated. Conclusion Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.

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