Survival in metastatic castration resistant prostate cancer (mCRPC) trial participants.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
Carmel Jo Pezaro ◽  
Aurelius Gabriel Omlin ◽  
Deborah Mukherji ◽  
Diletta Bianchini ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Data ◽  
Cox Model ◽  
Performance Status ◽  
Specific Antigen ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Base Management

e15136 Background: Median overall survival (mOS) in patients (pts) with metastatic prostate cancer progressing despite castrate levels of testosterone (mCRPC) was 13-16 months (m) in the pre-docetaxel era. These data, obtained from clinical trials, were used to construct currently available prognostic nomograms. We hypothesise that these models no longer reflect survival. Pts and physicians urgently require updated prognostic data on which to base management decisions. Methods: Pts with mCRPC treated on phase I-III trials at our institution were identified and data retrospectively collected. Predicted survival by Halabi and Smaletz nomograms were compared to calculated survival using Kaplan-Meier analysis. Cox model multivariate (MV) analysis used variables at referral, including performance status (PS), Gleason (GS), prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin (Hb), visceral disease and albumin. Results: 423 pts with CRPC treated between 2003 and 2011 were included. At diagnosis median age was 62 years (y; 41.8 – 82.7); 226 (53.4%) had metastatic disease. Median interval from diagnosis to CRPC was 2.7y (0.2 – 21.7). At referral 248 pts (58.6%) were chemotherapy-naïve. Halabi and Smaletz models predicted mOS in chemo-naïve pts of 21m and 18m respectively, however the observed mOS was 32m (95%CI 28 – 38). Survival from CRPC was 43m (CI 37 – 46) and 39m (CI 34 - 44) in pre- and post-chemo pts, respectively. Conclusions: Despite aggressive disease characteristics, our pts lived significantly longer than predicted by current nomograms. MV analysis confirmed the importance of several previously identified prognostic factors. Survival data from this large cohort of CRPC pts should encourage men considering clinical trial participation. Previously developed nomograms no longer accurately predict survival.

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.

Dynamic changes of alkaline phosphatase as surrogate for best clinical benefit and overall survival during very early abiraterone therapy compared to PSA-changes in bone metastatic castration resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 260-260
Author(s):  
Martin Boegemann ◽  
Phillip Mikah ◽  
Okyaz Eminaga ◽  
Edwin Herrmann ◽  
Philipp Marius Papavassilis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Clinical Benefit ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Dynamic Changes ◽  
Castration Resistant ◽  
Kaplan Meier

260 Background: Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under Abiraterone acetate (AA). ALP-Bouncing can be observed during very early AA-therapy. Methods: Men with bone mCRPC (bmCRPC) on AA 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit (BCB) and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. Results: 39 pre- and 45 post-chemotherapy patients with median follow up of 14.0 months were analyzed. In univariate analysis failure of PSA-reduction ≥50% (PSA-red≥50%) and failure of ALP-Bouncing were the strongest predictors of progressive disease (p=0.003 and 0.021). Rising ALP at 12 weeks (ALP12), no PSA-red≥50% and no ALP-Bouncing were strongest predictors of poor OS, (all p<0.001). Kaplan-Meier-analysis showed worse OS for ALP12, no PSA-red≥50% and no ALP-Bouncing (p<0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, no PSA-red≥50% and ALP12 being the strongest (p<0.001). In multivariate analysis PSA-red≥50% remained independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (p=0.014). No patient with ALP-Bouncing had PD for BCB. Patients with ALP12 had no further benefit of AA. Conclusions: Dynamic changes of ALP, LDH and PSA during AA-therapy are associated with BCB and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes and rising ALP12 under AA may help to decide whether to discontinue AA.

CTC counts as a biomarker of prognosis and response in metastatic castration-resistant prostate cancer (mCRPC) from the CARD trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 161-161
Author(s):  
Johann S. De Bono ◽  
Klaus Pantel ◽  
Eleni Efstathiou ◽  
Cora N. Sternberg ◽  
Daniel Castellano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Response ◽  
Cox Model ◽  
Specific Antigen ◽  
Continuous Variable ◽  
Shannon Index ◽  
Response To Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Objective Tumor Response

161 Background: In the prospective CARD trial (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer who had received docetaxel and progressed within 12 months with the alternative androgen-signaling-targeted inhibitor. Here we analyzed circulating tumor cell (CTC) counts as a biomarker of prognosis and response to therapy. Methods: Blood samples collected at screening (SC), Cycle 2 (C2) Day 1, and end of therapy were sent to Epic Sciences for CTC analysis. The association between CTC counts, defined as any cytokeratin-positive, CD45-negative cell, and clinical outcomes were pre-specified and analyzed using a multivariate Cox model for time-to-events (rPFS, OS) or a Χ2 test for categorical outcomes (objective tumor response). Results: Of the 255 patients randomized, 237 (92.9%) had evaluable samples at SC and 213 (83.5%) at C2. CTCs ≥ 1 were detected in 204 samples at SC (86%) and 178 samples at C2 (84%), with a median (interquartile range) count per mL of blood of 4.1 (1.3–14.2) and 5.2 (1.5–17.3), respectively. At baseline, higher CTC counts were associated with higher values of lactate dehydrogenase (P = 0.014), alkaline phosphatase (P < 0.001), and prostate-specific antigen (P < 0.001). High CTC counts, measured as a continuous variable at SC (all arms combined) were associated with a shorter OS (P = 0.03), but not rPFS (P = 0.7). However, favorable changes in absolute CTC count from SC to C2, all arms combined, were associated with longer rPFS (P = 0.03). Conversion from high (≥ 3) to low (< 3) CTC count at C2 or maintenance of a low CTC count at C2 was associated with objective tumor response (P = 0.007). Analysis of the associations of CTC androgen receptor variant 7, chromosomal instability, heterogeneity status (Shannon Index), single-cell genotypes (e.g. retinoblastoma/phosphatase and tensin homolog copy-loss), and the presence of CTCs with small-cell/neuroendocrine morphology is ongoing. Conclusions: This preplanned analysis of the CARD trial confirms that baseline CTC counts, measured by Epic Sciences platform, are prognostic. Moreover, early favorable changes in CTC counts from baseline to C2 are associated with response to therapy. Funding: Sanofi. Clinical trial information: NCT02485691.

scholarly journals A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
One Year

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

scholarly journals Efficacy and Safety of Docetaxel in Elderly Patients With Metastatic Castration-Resistant Prostate Cancer

2018 ◽  
pp. 1-9 ◽  
Author(s):  
Manuel Caitano Maia ◽  
Allan A. Lima Pereira ◽  
Liana Valente Lage ◽  
Natalia Moreno Fraile ◽  
Victor Van Vaisberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Line Chemotherapy

Purpose Limited data are available about the tolerability and clinical outcomes of elderly patients with metastatic castration-resistant prostate cancer (mCRPC) who are treated with docetaxel. We evaluated the efficacy and safety of docetaxel as first-line chemotherapy for patients with mCRPC who were treated in our institution. Materials and Methods We retrospectively identified patients with mCRPC and a Karnosfky performance status of 60% or greater treated with docetaxel on any schedule as first-line chemotherapy between 2008 and 2013. The primary end point was a comparison of median overall survival (OS) according to age in this population. Secondary end points were comparisons of the rates of severe toxicities, prostate-specific antigen (PSA) decline of 50% or greater, and time to progression (TTP). Results were stratified by three age groups: younger than 65 years, 65 to 74 years, and 75 years or older. Results Among the 197 patients included, 68 (34%) were younger than 65 years, 85 (43%) were 65 to 74 years, and 44 (22%) were 75 years or older. The mean number of comorbidities was not different among groups (1.19 v 1.32 v 1.43; P = .54). Patients younger than 65 years received a higher cumulative dose of docetaxel (450 mg/m2 v 382 mg/m2 v 300 mg/m2; P = .004). The rates of PSA decline of 50% or greater (41% v 47% v 36.4%; P = .51) and the median TTP (5.13 v 5.13 v 4.7 months; P = .15) were comparable among all groups. The median OS was longer in the group of patients younger than age 65 years (19.6 v 12.4 v 12.3 months; P = .012). Rates of any grade 3 or higher adverse event were not different among groups (63.2% v 71.8% v 54.5%; P = .14). Conclusion Administration of docetaxel in elderly patients who had good performance status was well tolerated. Rates of PSA decline and TTP were similar to those of younger patients, but median survival was lower.

Randomized Phase II Study of Docetaxel and Prednisone With or Without OGX-011 in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4247-4254 ◽  
Author(s):  
Kim N. Chi ◽  
Sebastien J. Hotte ◽  
Evan Y. Yu ◽  
Dongsheng Tu ◽  
Bernhard J. Eigl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Experimental Therapy ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin. Results Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87). Conclusion Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.

scholarly journals Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases

2021 ◽  
Vol 10 ◽  
Author(s):  
Qingfu Zhang ◽  
Yunan Han ◽  
Yao Zhang ◽  
Dan Liu ◽  
Jian Ming ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Stage Iv ◽  
Immunohistochemical Analysis ◽  
Prostate Adenocarcinoma ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Neuroendocrine Prostate Cancer

PurposeThis study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).Materials and MethodsWe collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate-specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.ResultsAmong the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 months, 95% CI: 15.3–19.9 months) had significantly worse survival compared with usual CRPC patients (median OS: 23.6 months, 95% CI: 21.3-25.9 months, log-rank P = 0.001), especially in metastasis cases (median OS: 15.7 months, 95% CI: 13.3-18.0 months) and patients with small cell carcinoma component (median OS: 9.7 months, 95% CI: 8.2–11.2 months). Prostate adenocarcinoma with diffuse NE differentiation (median OS: 18.8 months, 95% CI: 15.3–22.3 months) had poor outcome than those with usual CRPC (P = 0.027), while there was no significant change in the focal NE differentiation (median OS: 22.9 months, 95% CI: 18.1–27.7 months, P = 0.136). In the unadjusted model, an excess risk of overall death was observed in T-NEPC with PSA negative (HR = 2.86, 95% CI = 1.39–6.73). Among 476 NEPC cases in the SEER database from 2004 to 2017, we observed a higher hazard of overall death in patients aged 65 years and older (HR = 1.35, 95% CI = 1.08–1.69), patients with PSA ≤ 2.5 ng/ml (HR = 1.90, 95%CI = 1.44–2.52), patients with PSA 2.6–4.0 ng/ml (HR = 2.03, 95%CI = 1.38–2.99), stage IV tumor (HR = 2.13, 95%CI = 1.47–3.08) and other races (HR = 1.85, 95%CI = 1.17–2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.ConclusionT-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.

scholarly journals Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 526
Author(s):  
Taizo Uchimoto ◽  
Kazumasa Komura ◽  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Kazuhiro Takahashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Performance Status ◽  
Specific Antigen ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Primary Resistance ◽  
Castration Resistant ◽  
First Line Treatment

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Impact of number of lines of therapy following docetaxel (D) in metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Guru Sonpavde ◽  
Menaka Bhor ◽  
Daniel Hennessy ◽  
Debajyoti Bhowmik ◽  
Liji Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alkaline Phosphatase ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Drug Group ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
The Impact

223 Background: The impact of number of lines of therapy on outcomes following docetaxel (D) in metastatic castration-resistant prostate cancer (mCRPC) is unclear. We examined outcomes with cabazitaxel (C) and/or abiraterone acetate (A), following D during a period when all three therapies were available. We previously reported that most patients received only two of these three therapies. Among patients who received all three, DCA was administered more commonly and exhibited better overall survival (OS) than DAC after controlling for prognostic factors. Here, we report the impact of number of lines of therapy following D. Methods: A retrospective analysis of the U.S. Oncology network electronic health records (EHR) was conducted of post-D patients with mCRPC who received C and/or A from April 2011 to May 2012. Median OS was analyzed by Kaplan-Meier method. Cox proportional hazard models were used to evaluate impact on OS of number of therapies administered, age, Prostate Cancer Working Group (PCWG2) subtype, Charlson comorbidity index, prostate-specific antigen (PSA), alkaline phosphatase, hemoglobin, narcotic use, and treatment duration. Results: Multivariate analysis showed significantly lower mortality in the three-drug group compared to the two-drug group (HR 0.209 95% CI: 0.092-0.476, p<0.05). 113 patients received three drugs (DCA=77, DAC=36) and 237 received two drugs (DA=183, DC=54). The three-drug cohort was significantly younger than the two-drug group (median age 69 vs. 73). Other significant covariates (p<0.05) for mortality were narcotic use (HR 2.010 [1.240-3.259]), PSA (HR 1.014 [1.001-1.027] and alkaline phosphatase (HR 1.001 [1.000-1.001]. Conclusions: In men with mCRPC receiving C and/or A post-D, patients receiving all three therapies were younger and exhibited significantly better OS after controlling for clinical factors. In those receiving only two therapies, there appeared to be no difference in outcomes for second-line C versus A. Given the favorable impact of receiving all three therapies, more frequent administration of DCA in the three-drug group and better OS for DCA compared to DAC, we hypothesize that DCA may be a more optimal sequence. These results are exploratory and prospective validation is necessary.

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