scholarly journals 177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study)

2021 ◽  
Author(s):  
Fadi Khreish ◽  
Zaidoon Ghazal ◽  
Robert J. Marlowe ◽  
Florian Rosar ◽  
Amir Sabet ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Baseline Serum ◽  
Castration Resistant ◽  
Patient Reported ◽  
End Stage

Abstract Purpose Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice. Methods We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late–end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan–Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum–maximum) values are given. Results Patients received 3 (1–13) 177Lu-PSMA-617 activities (6.5 [2.5–11.6] GBq/cycle) every 5.7 (3.0–11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4–6.6) months and OS, 14.5 (95%CI 11.5–17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5–5.5], p < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%). Conclusions In a large, prospectively observed “real-world” cohort with late-stage/end-stage mCRPC and conventional treatment failure, 177Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.

Early change in prostate-specific antigen levels as a predictive marker for overall survival during vintage hormonal therapy for metastatic hormone-sensitive prostate cancer

2020 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Proportional Hazards ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Hormone Sensitive

Abstract Background The effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients has not been well investigated. Here, we evaluated the effect of factors that lead to castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC. Methods Medical records of 71 consecutive primary mHSPC patients treated with ADT were analyzed. Factors predicting the time to CRPC and OS in these patients were evaluated at 3 months after ADT induction. Results The median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis using Cox proportional hazards regression, a Gleason score of 8 or more (p = 0.004), extent of disease value (EOD) of 2 or more (p = 0.004), and a PSA level of 1% or more of the pretreatment levels after 3 months of ADT (p = 0.017) were independent predictors of shorter time to CRPC. For OS, a PSA level of 1% or more after 3 months of ADT was the independent predictor (p = 0.004). Conclusion % PSA was an important factor that correlated with poor prognosis at 3 months after ADT induction.

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.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

scholarly journals End Points and Outcomes in Castration-Resistant Prostate Cancer: From Clinical Trials to Clinical Practice

2011 ◽  
Vol 29 (27) ◽  
pp. 3695-3704 ◽  
Author(s):  
Howard I. Scher ◽  
Michael J. Morris ◽  
Ethan Basch ◽  
Glenn Heller
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
Disease Status ◽  
Castration Resistant Prostate Cancer ◽  
End Points ◽  
New Therapeutic Approaches ◽  
Castration Resistant ◽  
Patient Reported ◽  
Early Phase Clinical Trials

New therapeutic approaches for castration-resistant prostate cancer (CRPC) introduce new treatment dilemmas: how best to sequence these options to maximally benefit patients, what tests to perform before and after treatment to assess disease status, and how to interpret the test results and use them to guide treatment. New and specific end points for different classes of drugs are needed to provide the information to guide these treatment decisions. In 2008, the Prostate Cancer Working Group 2 consensus criteria for early-phase clinical trials redefined clinical trial end points as first, to control, relieve, or eliminate disease manifestations present when treatment is started and second, to prevent or delay future disease manifestations. Disease manifestations include prostate-specific antigen (PSA), soft-tissue disease (nodes and/or viscera), bone disease (most common site of spread), and symptoms. Recent US Food and Drug Administration (FDA) approvals for CRPC therapies have been based on the prevent/delay end points that reflect unequivocal benefit to a patient: prolongation of life or reduction in skeletal-related events (SREs). For the practicing oncologist, the control/relieve/eliminate outcomes should serve primarily to inform the decision of whether to continue therapy. In this review, we consider individual end points such as PSA, imaging, and patient-reported outcomes in the context of the control/relieve/eliminate and prevent/delay framework. We address the time-to-event end points of metastasis prevention, SRE, time to progression, and overall survival in the context of regulatory approvals. We also discuss circulating tumor cells measured with the CellSearch assay, recently cleared by the FDA for monitoring CRPC.

Update on radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: clinical aspects and survival effects

2021 ◽  
pp. 030089162110377
Author(s):  
Valentina Fuoco ◽  
Giovanni Argiroffi ◽  
Stefania Mazzaglia ◽  
Alice Lorenzoni ◽  
Valentina Guadalupi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Current Data ◽  
Phase Iii ◽  
Current Evidence ◽  
Clinical Aspects ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Treatment Protocols ◽  
Castration Resistant

Objective: To give an updated overview on clinical aspects and survival effects of lutetium-177–prostate-specific membrane antigen (PSMA) (177Lu-PSMA) radioligand therapy (RLT), a novel treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: PubMed/MEDLINE database was searched for relevant articles published up to March 2021. The search was restricted to English-language articles. Results: Current evidence from the literature consistently demonstrated the efficacy, safety, and survival benefit of 177Lu-PSMA RLT in mCRPC. However, current data rely predominantly on retrospective analyses, showing heterogeneity of patient population and treatment protocols. More recently, results from the first randomized phase II study (TheraP) demonstrated that 177Lu-PMSA therapy significantly improved prostate-specific antigen response rate (66% vs 37%) and had fewer grade 3/4 adverse events when compared to cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC. This review is intended to provide an updated overview of treatment protocols and responses, toxicity profile, and survival effects of 177Lu-PSMA RLT. Conclusions: 177Lu-PSMA RLT has emerged as a promising targeted treatment in mCRPC. It is currently applied in compassionate use programs and following exhaustion of approved therapies. Crucial for establishing this treatment in routine clinical management will be the results of the phase III VISION trial, which may confirm the encouraging patient outcomes reported to date.

Association of very small nuclear circulating tumor cell (vsnCTC) with clinical outcomes in metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 168-168
Author(s):  
Jasmine Jiemei Wang ◽  
Pai-Chi Teng ◽  
Yu Jen Jan ◽  
Jie-Fu Chen ◽  
Galen Cook-Wiens ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pre Treatment

168 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We proposed vsnCTCs as a putative biomarker of a lethal subtype in metastatic castration resistant PC (mCRPC). Methods: In this study, 76 patients with mCRPC were recruited for overall survival (OS) analysis. Of the 76 patients, 47 had available pre-treatment blood specimens prior to the initiation of androgen receptor signaling inhibitor (ARSI, e.g. abiraterone and enzalutamide) or taxane therapy. Using the NanoVelcro CTC Assay, CTCs were captured and subjected to immunofluorescence staining. CTCs were identified as DAPI+/CK+/CD45- with a round or oval nucleus. Additionally, CTC nuclear size was measured and defined as the square root of the product of the long axis and the short axis. Kaplan-Meier analysis and Cox proportional hazards model were conducted. Results: Patients with vsnCTC (i.e., vsnCTC+) had a significantly shortened OS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n=49) vs. 149 (vsnCTC-, n=27) weeks (log-rank HR=2.6 with 95% CI 1.5 to 4.5, p=0.0006). Progression free survival (PFS) analysis was performed for the 47 patients with pre-treatment blood samples. The median PFS was 14 (vsnCTC+, n=29) vs. 26 (vsnCTC-, n=18) weeks (log-rank HR=2.2 with 95% CI 1.2 to 3.9, p=0.0069). We also found that the hazard ratio of overall survival increased significantly as the CTC nuclear size decreased using the p spline plot. Conclusions: Our study showed that nuclear size reduction has importance in CTCs in a fashion similar to its utility in tissue. This study points toward the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for morality. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC. This has potential importance in optimizing therapeutic choices.

scholarly journals Serum Androgens As Prognostic Biomarkers in Castration-Resistant Prostate Cancer: Results From an Analysis of a Randomized Phase III Trial

2013 ◽  
Vol 31 (22) ◽  
pp. 2791-2798 ◽  
Author(s):  
Charles J. Ryan ◽  
Arturo Molina ◽  
Jinhui Li ◽  
Thian Kheoh ◽  
Eric J. Small ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Short Form ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Baseline Serum ◽  
Castration Resistant

Purpose In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS. Patients and Methods COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median. Results Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens. Conclusion SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.

scholarly journals The development and validation of a prognostic nomogram and nomogram application software among men treated with abiraterone acetate and/or enzalutamide for metastatic castration-resistant prostate cancer

2020 ◽  
Author(s):  
Takashi Kawahara ◽  
Yusuke Saigusa ◽  
Shuko Yoneyama ◽  
Masashi Kato ◽  
Ippei Kojima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Mobile App ◽  
Application Software ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Abstract BACKGROUND:With widespread medication choices for metastatic castration-resistant prostate cancer (mCRPC) is now available, on the other hand biomarker to predict the efficacy of each mCRPC treatment has not been established.Objective:This study developed prognostic nomogram to predict prognosis in CRPC patients who received abiraterone acetate (ABI) and/or enzalutamide (ENZ).Design, Setting, and Participants:A total of 568 mCRPC patients received ABI and/or ENZ from 2012 to 2017 were enrolled in this study. We developed prognostic nomogram based on the risk factors by Cox proportional hazards regression model.Outcome Measurements and Statistical Analysis:The nomogram was also assessed for discriminatory ability with the concordance index (C-index). We repeated 5-fold cross-validation 2000 times to estimate the C-index and reported the means of the estimated C-index for the training and validation sets. And we also developed nomogram application software (app) based on this nomogram.Results and Limitations:The median overall survival (OS) was 24.7 months. A multivariable analysis showed that the time to CRPC, pre-chemotherapy, baseline PSA, baseline ALP, and baseline LDH were independent risk factors for the OS (HR: 0.521, 1.681, 1.439, 1.827, 12,123, p:0.001, 0.001, <0.001, 0.019, <0.001)). C-index was 0.72 in training cohort and 0.71 in validation cohort.CONCLUSIONS:We developed nomograms to predict the OS for Japanese mCRPC patients who received ABI and/or ENZ. The advent of mCRPC prognosis prediction app will facilitate greater accessibility for clinical use.Patient SummaryThis study developed and validated a nomogram for predicting the prognosis of mCRPC patients who receive ABI/ENZ treatment using clinical information. This study also developed mobile app to facilitate clinical usage.

scholarly journals Oncological outcomes of metastatic castration resistant prostate cancer (mCRPC) treated with different therapies sequences after completion of docetaxel: a retrospective study in Songklanagarind Hospital

2021 ◽  
Vol 42 (2) ◽  
pp. 131-137
Author(s):  
Isaris Chaokhamin ◽  
◽  
Worapat Attawettayanon ◽  
Virote Chalieopanyarwong ◽  
Monthira Tanthanuch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Oncological Outcomes ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy

Objective: Many treatment options of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy have proved efficacious in clinical trials but, to date, knowledge regarding oncological outcomes is limited. Materials and Methods: We assessed the oncological outcome of 4 drugs (abi- raterone acetate, cabazetaxel, enzalutamide and ketoconazole) in a normal clinical setting in a university-based hospital. Our cohort consisted of 69 patients with post-docetaxel mCRPC. The primary endpoint was overall survival (OS). The secondary endpoint was predicted factor associated overall survival with all sec- ond-line mCRPC treatment outcomes according to the Cox proportional hazards regression model. Results: This cohort consisted of 69 patients with progressive mCRPC after docetaxel chemotherapy. Median overall survival following treatment with abiraterone acetate and ketoconazole was 25.92 and 9.59 months respectively (p < 0.05). Overall survival rates at 1-year following abiraterone acetate, cabazetaxel, enzalutamide and ketoconazole therapy were 76.3%, 83.3%, 100% and 41.9%, respectively. Multivariable analysis found that abiraterone acetate, cabazitaxel and enzalutamide significantly improved survival in comparison to ketoconazole (p < 0.001). Conclusion: Analysis of overall survival following second-line treatment of mCRPC post docetaxel in our study statistically significantly confirmed that abiraterone acetate, cabazitaxel and enzalutamide improve overall survival in comparison to ketoconazole. The study also found that enzalutamide treatment resulted in better outcomes in comparison to the other drugs.

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