Experience with sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) with visceral spread from PROCEED.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 174-174
Author(s):  
Nicholas J. Vogelzang ◽  
Philip W. Kantoff ◽  
Mark C. Scholz ◽  
Jeffrey L. Vacirca ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Cellular Immunotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant ◽  
Visceral Metastases ◽  
Antigen Presenting ◽  
Post Hoc ◽  
Clinical Trial Information

174 Background: Trials of approved agents in mCRPC have reported shorter overall survival (OS) in men with visceral metastases (mets). The phase 3 IMPACT trial evaluated sipuleucel-T, an autologous cellular immunotherapy, in mCRPC but excluded visceral mets. PROCEED, a registry of mCRPC patients receiving sipuleucel-T, offers the first description of sipuleucel-T in patients with visceral mets. Methods: PROCEED enrolled men with mCRPC treated with sipuleucel-T biweekly x 3. Dose adjustment for organ dysfunction was unnecessary. Men were followed until death, study withdrawal, or a minimum of 3 years. OS is reported in this post-hoc subgroup analysis. Results: 1902 men received ≥1 sipuleucel-T infusion between 2011-2014. Visceral mets (n = 90) included liver (n=21), lung (n=61), and brain (n=2) involvement. Compared to patients without visceral mets (Table), men with visceral mets had poorer performance status (PS) and higher baseline prostate-specific antigen (PSA). Median OS was 20.5 and 31.2 mo in those with and without visceral mets. Patients with liver and lung mets had a median OS of 16.3 and 21.0 mo, respectively. Activation of antigen-presenting cells, a measure of immune activation and product potency, was similar in those with and without visceral mets. Conclusions: Initial observations suggest that patients with mCRPC and visceral spread can activate their immune cells to produce sipuleucel-T, but have a shorter OS than those with bone and/or lymph node spread. (NCT01306890). Clinical trial information: NCT00065442. [Table: see text]

Real-world experience with sipuleucel-T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel (D): Data from PROCEED.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 30-30 ◽  
Author(s):  
A. Oliver Sartor ◽  
Matthew R. Cooperberg ◽  
Nicholas J. Vogelzang ◽  
Mark Creamer Scholz ◽  
Raoul S. Concepcion ◽  
...  
Keyword(s):  
Real World ◽  
Performance Status ◽  
Phase Iii ◽  
Cellular Immunotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Multicenter Phase ◽  
Real World Setting ◽  
Clinical Trial Information

30^ Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC. The phase III IMPACT trial showed a significant improvement in overall survival with sipuleucel-T treatment (tmt). In IMPACT, D use was prohibited within 3 months prior to registration due to the potential immunosuppressive impact of chemotherapy. PROCEED is an ongoing, multicenter, phase 4 registry enrolling pts receiving sipuleucel-T in the real-world setting. Enrollment has no restrictions on D use; thus, data from PROCEED may help determine whether prior D affects sipuleucel-T manufacture. Here we present preliminary results on baseline demographics and product parameters in PROCEED subjects with and without prior D exposure. Methods: Pts who were treated with sipuleucel-T within the prior 6-months at clinical sites were asked to provide informed consent to participate in PROCEED. Results: By September 2012, 560 pts completed sipuleucel-T tmt; 15% previously received D (median 291 days prior to 1st sipuleucel-T infusion). Patients with prior D had higher PSA levels, and those with recent D use tended to have a lower performance status and higher Gleason scores, but product parameters were generally comparable between the groups (see table). Conclusions: Pts enrolled in PROCEED with and without prior D exposure had different baseline demographics and disease characteristics. However, sipuleucel-T product parameters were comparable regardless of prior D exposure. Clinical trial information: NCT01306890. [Table: see text]

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.

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.

Sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) patients ≥80 years-old: Data from PROCEED.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 64-64 ◽  
Author(s):  
Chadi Nabhan ◽  
A. Oliver Sartor ◽  
Matthew R. Cooperberg ◽  
Andrew J. Armstrong ◽  
Jeffrey L. Vacirca ◽  
...  
Keyword(s):  
Cellular Immunotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Pivotal Phase ◽  
Risk Of Death ◽  
Immune Parameters ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
High Prevalence ◽  
Antigen Presenting

64 Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC based on data from the pivotal phase 3 IMPACT trial that demonstrated a 22% reduction in the risk of death. Given the high prevalence of older men in the mCRPC patient (pt) population, we sought to understand disease characteristics and sipuleucel-T product parameters in pts ≥80 years (yrs). Methods: PROCEED is an ongoing phase 4 registry enrolling pts treated with sipuleucel-T within ≤6 months. Baseline pt demographics and disease characteristics were collected. Sipuleucel-T product parameters that were assessed included: total nucleated cell (TNC) count, antigen presenting cell (APC) count (large CD54+ cells), and APC activation (upregulation of CD54; a measure of product potency). Results: As of May 2013, 1254 subjects were enrolled and have completed treatment. Of these, 278 (20%) pts were ≥80 yrs-old. Disease and infused product characteristics in pts ≥80 yrs vs. <80 yrs are detailed in the table below. Product parameters appear similar between groups. Conclusions: In this large cohort of elderly pts ≥80 yrs treated prospectively with sipuleucel-T immunotherapy, we demonstrate that product parameters were similar to their younger counterparts (<80 years). This implies adequate immune up-regulation in elderly pts. Additional follow-up is needed to explore correlations between OS and various immune parameters in both groups. Clinical trial information: NCT01306890. [Table: see text]

Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 205-205 ◽  
Author(s):  
Scott T. Tagawa ◽  
David M. Nanus ◽  
Edwin M. Posadas ◽  
Daniel Peter Petrylak ◽  
Justine Yang Bruce ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Systemic Exposure ◽  
Abiraterone Acetate ◽  
Maximum Plasma ◽  
Castration Resistant Prostate Cancer ◽  
Time Curve ◽  
Castration Resistant ◽  
Psa Progression ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

205 Background: D and AA may have complementary mechanisms of action; coadministration may be beneficial. A phase Ib study assesses the safety of escalating doses of D + AA. Methods: Up to4 cohorts (C) of chemo-naïve mCRPC pts would receive D + AA. Data for C1 and C2 are presented. Primary end point: proportion of pts with dose-limiting toxicity (DLT) between Wks 2 and 7, defined as grade (Gr) ≥ 3 non-heme toxicity, Gr 4 neutropenia (absolute neutrophil count < 500/mm3) > 7 days (or febrile neutropenia), Gr 4 thrombocytopenia, or other intolerable toxicity. D + AA was deemed safe if ≤ 33% of pts experienced DLT. Pharmacokinetic (PK) parameters were evaluated for D and AA alone and in combination. Results: 15 pts were treated and 6 pts/C were evaluable for DLT assessment. 2 DLTs were observed in C1, and 1 in C2. 73% and 87% of pts had confirmed ≥ 90% and ≥ 50% prostate-specific antigen (PSA) decline, respectively. Median time to PSA progression has not yet been reached. Systemic exposure, based on maximum plasma concentration (Cmax) and area under the concentration–time curve [(AUC)∞ for D, AUC24 for abiraterone (ABI)], was comparable for both D and AA alone and for D + AA. 3 pts in C3 (D 75 mg/m2+ AA 1000 mg) have been treated past Wk 7 without DLT. Conclusions: D + AA was well tolerated in the cohorts tested. Preliminary results justify further evaluation of safety and efficacy in additional Cs. Clinical trial information: NCT01400555. [Table: see text]

Clinical outcomes and safety in men ≥ 75 and < 75 years with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in the phase 3 PREVAIL trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Julie Nicole Graff ◽  
Giulia Baciarello ◽  
Andrew J. Armstrong ◽  
Celestia S. Higano ◽  
Peter Iversen ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Treatment Safety ◽  
The Impact

200 Background: In the phase 3 PREVAIL trial, enzalutamide (ENZA), an androgen receptor inhibitor, improved overall survival (OS) and radiographic progression-free survival (rPFS) relative to placebo (PBO) in chemotherapy-naïve men with mCRPC. Methods: PREVAIL randomized 1,717 patients (pts) with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC 1:1 to ENZA 160 mg daily or PBO. Coprimary endpoints were OS and rPFS. This prespecified analysis evaluated the impact of age (≥ 75 vs < 75 years) on efficacy and safety. Results: In PREVAIL, 609 (35%) pts were aged ≥ 75 years. This older subset had several poorer baseline prognostics relative to those aged < 75 years: worse ECOG performance status (ECOG 1: 45.0% vs 24.7%), higher prostate-specific antigen (PSA; 73.3 vs 37.3 ng/mL) and more cardiovascular disease (26.9% vs 16.5%). In both older and younger pts, ENZA improved OS, rPFS and time to PSA progression (Table). Pts aged ≥ 75 years in both the ENZA and PBO groups combined had a higher rate of grade ≥ 3 adverse events (46% vs 37% in younger pts) and among enzalutamide-treated men more older pts reported falls (any grade; ENZA 19% and PBO 8%) than younger pts (ENZA 7% and PBO 4%). Fewer pts ≥ 75 years received subsequent antineoplastic therapies. Conclusions: In PREVAIL, efficacy outcomes in elderly (≥ 75 years) and younger (< 75 years) pts with chemotherapy-naïve mCRPC were comparable and pts consistently benefited from ENZA treatment. Safety with ENZA was similar in both age groups, although older pts reported a higher incidence of falls and received fewer subsequent antineoplastic therapies. Clinical trial information: NCT01212991. [Table: see text]

Sequential use of new agents (NAs) after docetaxel (DOC) first line in metastatic castration-resistant prostate cancer (mCRPC) patients (pts): A pooled-analysis of the published studies.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 258-258 ◽  
Author(s):  
Francesca Maines ◽  
Orazio Caffo ◽  
Antonello Veccia ◽  
Emilio Bria
Keyword(s):  
Performance Status ◽  
Analysis Data ◽  
Pooled Analysis ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Visceral Metastases ◽  
Single Strategy ◽  
Selection Factors

258 Background: NAs have recently demonstrated a survival advantage in mCRPC pts progressing after DOC: two hormonal NAs (HNA), abiraterone and enzalutamide, and one chemotherapeutic agent, cabazitaxel (CAB). Recent evidences of possible cross-resistance has opened a debate about the best strategy when these drugs are used sequentially. We performed a pooled analysis of the published studies in order to assess if one of the following sequence strategy was potentially better than the others: a) HNA→ HNA, b) HNA → CAB or c) CAB → HNA. Methods: We evaluated the studies reporting clinical outcomes of a single NA administered after sequential treatment with docetaxel followed by another NA in mCRPC pts. All studies reporting monthly overall survival (OS) rates were considered eligible for the analysis; data were extracted, cumulated and weighted by taking into account each trial sample. We also evaluated possible differences in terms of factors able to produce potential patient-selection biases (age, Performance Status, visceral metastases and Gleason score). Results: Ten retrospective studies met the selection criteria of our analysis. They reported the outcomes of 735 pts who have received HNA → HNA (320 pts), HNA→ CAB (249 pts), and CAB → HNA (166 pts). No statistically significant differences were observed in terms of selection factors. Cumulative OS rates (with CIs), according to treatment sequence, are summarized in the Table. Conclusions: Our data seems to confirm a potential cumulative survival benefit of sequential use of NAs without a clear superiority of a single strategy over the others after DOC first-line in mCRPC patients. This conclusion is tempered by the retrospective nature and the potential selection biases. Nevertheless, a possible OS advantage could be observed when a CAB-based sequence is adopted. [Table: see text]

KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Mark N. Stein ◽  
Lawrence Fong ◽  
Anthony E. Mega ◽  
Elaine Tat Lam ◽  
John W. Heyburn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase 1 ◽  
Specific Antigen ◽  
Prior Exposure ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinical Trial Information

126 Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x109 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta <50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.

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