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]

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.

PROfound: A randomized Phase III trial evaluating olaparib in patients with metastatic castration-resistant prostate cancer and a deleterious homologous recombination DNA repair aberration.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5091-TPS5091 ◽  
Author(s):  
Johann S. De Bono ◽  
Maha Hussain ◽  
Antoine Thiery-Vuillemin ◽  
Joaquin Mateo ◽  
A. Oliver Sartor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Homologous Recombination ◽  
Radiographic Progression ◽  
Response Rate ◽  
Objective Response ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

TPS5091 Background: The median overall survival for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) is short. Available agents may offer limited therapeutic benefit, but no molecularly stratified treatment has yet been approved for this heterogeneous disease. A sizable percentage of pts with mCRPC has loss of function aberrations in genes involved in homologous recombination repair (HRR) in tumor tissue, such as BRCA1/2 and ATM. These aberrations can confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition. A Phase II study indicated that the oral PARP inhibitor olaparib (Lynparza) had antitumor activity in 33% of mCRPC pts who had progressed after new hormonal agent (NHA) treatment and chemotherapy, with a strikingly higher composite response rate in pts with a deleterious HRR gene aberration (HRRa) (88%; 14/16) vs pts without a HRRa (6%; 2/33) (Mateo et al.2015). The PROfound study evaluates olaparib efficacy and safety versus physician’s choice of either abiraterone acetate or enzalutamide, in pts with mCRPC and a HRRa (NCT02987543). Methods: To be eligible for this multinational, open-label, Phase III study, mCRPC pts must have progressed on prior NHA treatment and have a tumor HRRa in one of 15 genes, as confirmed by an HRR Assay (Foundation Medicine, Inc.). Cohort A (n = 240 approx) includes pts with mutations in BRCA1, BRCA2 or ATM, while pts with a mutation in 12 other HRR genes will be assigned to Cohort B (n = 100 approx). Pts will be randomized (2:1) to olaparib tablets (300 mg orally bid) or physician’s choice of either enzalutamide (160 mg orally od) or abiraterone acetate (1000 mg orally od with 5 mg bid prednisone) and treatment continued until radiographic progression (as assessed by blinded independent central review) or lack of treatment tolerability. The primary endpoint of radiographic progression-free survival (rPFS) will be assessed in Cohort A using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria. Key secondary efficacy endpoints include confirmed objective response rate, time to pain progression, overall survival (all Cohort A) and rPFS (both cohorts combined). Clinical trial information: NCT02987543.

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 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.

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

Phase III SYNERGY trial: Docetaxel +/- custirsen and overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and poor prognosis.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5009-5009 ◽  
Author(s):  
Kim N. Chi ◽  
Celestia S. Higano ◽  
Brent A. Blumenstein ◽  
James Andrew Reeves ◽  
Susan Feyerabend ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Integration of bone scan (BS) and computerized tomography (CT) findings as an endpoint to assess bone metastasis in metastatic castration-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 191-191
Author(s):  
Scott J. Parker ◽  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Anitha Alex ◽  
Marta Elise Heilbrun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastasis ◽  
Proportional Hazards ◽  
Statistical Significance ◽  
Cox Proportional Hazards ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Ct Findings ◽  
Significant Difference

191 Background: Progression of bone metastasis in mCRPC is assessed solely by BS findings and correlates modestly with overall survival (OS). Given the lack of reliability of BS findings and the ready availability of routinely performed CT scans, which commonly identify bone metastases, we aimed to better assess progression in bone by integrating BS and CT findings and to explore their association with OS. Methods: Data were obtained from patients treated at the University of Utah receiving docetaxel-based chemotherapy (D) or post-docetaxel therapy with orteronel (O). Patients with both baseline and on-therapy CT and BS within 90 days were eligible for analysis. CT and BS underwent central radiology review for bone lesions by a single radiologist. Progressive disease (PD) was defined as ≥ 1 new lesion. Survival was measured from start of therapy. Cox proportional hazards regression was used to explore potential prognosticators of overall survival (OS). Statistical significance was defined as 2-sided p < 0.05. Therapy was a stratification factor. Results: Twenty-eight patients were evaluable including 18 patients receiving D, and 10 receiving O post-docetaxel. The mean age of these patients was 71.4 years and median (95% CI) overall survival was 18.4 (9.7-35.4) months. Four patients had PD on both BS and CT, while 2 (7%) had PD on CT but not BS and 3 had PD on BS but not CT. Patients with PD on BS or CT had worse OS (HR = 2.68, 95% CI = 1.04-6.90, p = 0.041) than those with no PD on either CT or BS. Looking at individual lesions, 4 (14%) patients had new lesions identified on CT which was not observed using BS, and they were associated with worse OS (HR = 3.72, 1.01-13.66, p = 0.048). Conversely, no significant difference in OS was observed for 4 patients with lesions identified on BS which were not observed using CT (HR = 2.67, 0.58-12.32, p = 0.21). Conclusions: This hypothesis-generating study suggests that CT can complement and enhance the ability of BS to capture PD and predict OS. Integration of BS findings using Prostate Cancer Working Group (PCWG)-3 guidelines to define PD and CT bone findings should be investigated in a larger study as an intermediate endpoint.

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