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

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]

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Real-world experience with sipuleucel-T in patients (pts) ≥80 years old with metastatic castration-resistant prostate cancer (mCRPC): Data from PROCEED.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.131 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 131-131

Author(s):

Chadi Nabhan ◽

A. Oliver Sartor ◽

Matthew R. Cooperberg ◽

Jeffrey L. Vacirca ◽

Raoul S. Concepcion ◽

...

Keyword(s):

Phase Iii ◽

Cellular Immunotherapy ◽

Castration Resistant Prostate Cancer ◽

Immune Parameters ◽

Castration Resistant ◽

Disease Characteristics ◽

High Prevalence ◽

Impact of prior radiation treatment (tx) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.183 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 183-183

Author(s):

Steven E. Finkelstein ◽

Luke T. Nordquist ◽

Shaker R. Dakhil ◽

Nathan B. Green ◽

Elisabeth I. Heath ◽

...

Keyword(s):

Bone Metastases ◽

Real World ◽

Radiation Treatment ◽

Cellular Immunotherapy ◽

Castration Resistant Prostate Cancer ◽

The Real ◽

Risk Of Death ◽

Real World Setting ◽

Antigen Presenting

183 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Approval of sip-T was based primarily on the randomized, controlled, phase 3 study (IMPACT) that demonstrated a 22% reduction in the risk of death. Since radiation tx could suppress bone marrow function and therefore immune function, IMPACT excluded patients (pts) who received radiation more than or equal to 28 days prior to registration. PROCEED is an ongoing phase 4 registry enrolling pts tx with commercial sip-T in the real-world setting. Palliative radiation (PR) tx for bone pain prior to sip-T is not restricted in PROCEED, so the effects of prior radiation on sip-T manufacturing parameters can be evaluated. Methods: Pts treated with sip-T at or before six months were eligible. Baseline pt demographics and disease characteristics were collected. Sip-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: Data were available for 1,244 pts enrolled by May 2013, who completed tx; of those, 112 (9.0%) pts received PR to bone metastases prior to sip-T and 517 (41.6%) pts had no prior radiation of any kind (NRT). To ensure that groups (grp) were homogeneous and to limit the comparison of NRT pts with those who had PR only for bone metastases, pts with radical prostatectomy were isolated from each grp for further study, resulting in 44 pts in the PR grp and 159 pts in the NRT grp. Median cumulative APC counts were similar between grp, however TNC counts (PR: 9.89 vs. NRT: 12.09 x 109; P=0.002) and APC activation (PR: 34.2 vs. NRT: 38.5; P=0.048) were lower in the PR grp. However, the percentage of pts receiving all three infusions in each group was comparable (PR: 93.2% vs NRT: 95.0%; P=0.71). Conclusions: In the real-world setting, there is no evidence that prior radiation inhibits successful production of sip-T. Although TNC counts and APC activation were lower, APC counts were comparable in radiation treated pts. Effects on in vivo post treatment immune measures are being collected prospectively in a companion trial called PRIME. Clinical trial information: NCT01306890.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.174 ◽

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]

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.30 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 30-30 ◽

Cited By ~ 2

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]

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First interim results of the Radium-223 (Ra-223) reassure observational study in metastatic castration-resistant prostate cancer (mCRPC): Safety and baseline (BL) characteristics of U.S. patients (Pts) by prior/concomitant treatment (Tx).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.233 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 233-233 ◽

Cited By ~ 1

Author(s):

Lauren Christine Harshman ◽

A. Oliver Sartor ◽

Timothy Richardson ◽

John Sylvester ◽

Daniel Y. Song ◽

...

Keyword(s):

Descriptive Analysis ◽

Concomitant Treatment ◽

Castration Resistant Prostate Cancer ◽

Pivotal Phase ◽

Castration Resistant ◽

Radium 223 ◽

Using Data ◽

Favorable Safety

233 Background: Ra-223, a targeted alpha therapy, extended survival and had a favorable safety profile at 3 years’ follow up in pts with mCRPC in the pivotal phase 3 ALSYMPCA trial. The maturing global, prospective, single-arm, observational REASSURE study, designed to evaluate long-term safety at 7 years’ follow up, enrolled pts with mCRPC with bone metastases planned to receive Ra-223. Methods: We performed a descriptive analysis of safety and BL characteristics of US pts according to prior or concomitant abiraterone/enzalutamide (abi/enza) or prior docetaxel/cabazitaxel (chemo) using data from the first planned interim analysis (pts receiving ≥1 Ra-223 dose; median follow up 8 mo). Results: 244 US pts were included; 80% had no prior chemo. Prior abi/enza and/or chemo pts had higher median BL PSA and were less likely to complete 5-6 doses (Table). Subgroups had similar median ALP, LDH and Hb. Overall, drug-related tx-emergent AEs occurred in 71 pts (29%) and serious AEs in 9 (3.7%). Most common AEs were diarrhea, fatigue and anemia. AE incidence was numerically higher in pts who received prior chemo and/or abi/enza. Clinical trial information: NCT02141438. Conclusions: To date, REASSURE has not revealed any new safety findings and most pts complete 5-6 Ra-223 doses in routine US clinical practice. Pts with prior tx lines had lower Ra-223 tx completion and higher AE incidence, likely reflecting greater disease burden, as evidenced by higher median BL PSA.[Table: see text]

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Clinical drivers for imaging testing in nonmetastatic castration-resistant prostate cancer: May they be optimized?—Data of “IDENTIFICA” study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.318 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 318-318

Author(s):

Eduardo Useros RodrÃguez ◽

Álvaro Juárez ◽

Joaquín Carballido Rodríguez ◽

Jose Rubio ◽

Alfredo Rodríguez Antolín ◽

...

Keyword(s):

Prostate Cancer ◽

Critical Event ◽

Castration Resistant Prostate Cancer ◽

Significant Relation ◽

Curative Intent ◽

Castration Resistant ◽

Disease Characteristics ◽

Relevant Factors ◽

Rule Out

318 Background: Metastases (M+) detection is a critical event in non-metastatic castration-resistant prostate cancer (nmCRPC), as it entails a change in PC management and is a potential surrogate for survival at this stage. PSA doubling time (PSA-DT) has been described as a prognostic factor to develop M+. However, there could be other relevant factors to raise suspicion of progression in nmCRPC patients. The “IDENTIFICA” study tries to describe disease characteristics and clinical drivers that make physicians suspect the presence of M+ in nmCRPC patients in clinical practice in Spain. Methods: Observational, transversal, multicenter study. nmCRPC patients with physician’s suspiction of M+ were selected. Imaging tests to rule out metastases were requested; clinical drivers were described, along with clinical data related to prostate cancer (PC). Results: 197 nmCRPC patients were recruited (Jan-Jun 2018). Median age was 81.3 years. Median time from the onset of androgen deprivation therapy (ADT) to CRPC was 5.1 years (IQR: 2.5-8.2). ADT was the first PC treatment for 64.4% of , while 41.2% went through a curative-intent treatment. Median PSA-DT at CRPC diagnosis was 7.5 months. Time from PC diagnosis to CRPC was influenced by Gleason score at diagnosis ( p=0.001), primary curative intent treatment ( p<0.001), and PSA-DT at CRPC diagnosis ( p=0.04). Most important clinical drivers leading physicians to request imaging were PSA value, PSA-DT and PC guidelines recommendations. M+ were detected in 23 patients (16.5%). In the multivariate analysis, there was a statistically significant relation between positive imaging and time on ADT (OR 1.16; 95% CI 1.018-1.325; p=0.026) and time on CRPC status (OR 1.55; 95% CI 1.038-2.302; p=0.032). In this interim analysis, PSA and PSA-DT seemed not to be statistically related to M+ appearance. Conclusions: PSA and PSA-DT seem to be the most influential drivers to request imaging tests during follow-up of nmCRPC patients. Time on ADT and time on CRPC status could be relevant factors for M+ detection and phycisians should be aware of them and not just PSA or PSADT to properly ask for imaging tests.

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Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5514 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5514-5514 ◽

Cited By ~ 15

Author(s):

Karim Fizazi ◽

Neal D. Shore ◽

Teuvo Tammela ◽

Albertas Ulys ◽

Egils Vjaters ◽

...

Keyword(s):

Safety Profile ◽

Final Analysis ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Primary Analysis ◽

Risk Of Death ◽

Castration Resistant ◽

Secondary Endpoints ◽

Favorable Safety

5514 Background: DARO is a structurally distinct androgen receptor inhibitor with a favorable safety profile, approved for treating men with nmCRPC after demonstrating significantly prolonged metastasis-free survival, compared with placebo (PBO), in the phase III ARAMIS trial: median 40.4 vs 18.4 months, respectively (HR 0.41; 95% CI 0.34–0.50; P<0.0001). We report final analyses of OS and prospectively collected, patient-relevant secondary endpoints, and updated safety results. Methods: 1509 patients (pts) with nmCRPC were randomized 2:1 to DARO 600 mg twice daily (n=955) or PBO (n=554) while continuing ADT. Secondary endpoints included OS, and times to pain progression, first cytotoxic chemotherapy, and first symptomatic skeletal event. The OS analysis was planned to occur after approximately 240 deaths. Secondary endpoints were evaluated in a hierarchical order. Results: Final analysis was conducted after 254 deaths were observed (15.5% of DARO and 19.1% of PBO patients). After unblinding at the primary analysis, 170 pts crossed over from PBO to DARO. DARO showed a statistically significant OS benefit corresponding to a 31% reduction in the risk of death compared with placebo. All other secondary endpoints were significantly prolonged by DARO (Table), regardless of the effect of crossover and subsequent therapies on survival benefit. Incidences of treatment-emergent adverse events (AEs) with ≥5% frequency were generally comparable between DARO and PBO, similar to the safety profile observed at the primary analysis. Incidences of AEs of interest (including falls, CNS effects, and hypertension) were not increased with DARO compared with PBO when adjusted for treatment exposure. AEs in the crossover group were consistent with those for the DARO treatment arm. Conclusions: DARO showed a statistically significant OS benefit for men with nmCRPC. In addition, DARO delayed onset of cancer-related symptoms and subsequent chemotherapy, compared with PBO. With extended follow-up, safety and tolerability were favorable and consistent with the primary ARAMIS analysis (Fizazi et al, N Engl J Med 2019;380:1235-46). Clinical trial information: NCT02200614 .[Table: see text]

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Disease characteristics and outcome of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received a beta emitter (177Lu-PSMA) after an alpha emitter (radium-223).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17592 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17592-e17592

Author(s):

A. Oliver Sartor ◽

Christian la Fougère ◽

Markus Essler ◽

Samer Ezziddin ◽

Gero Kramer ◽

...

Keyword(s):

Castration Resistant Prostate Cancer ◽

Investigational Agent ◽

Castration Resistant ◽

Disease Characteristics ◽

Radium 223 ◽

Alpha Emitter ◽

Metastatic Setting ◽

Grade 3 ◽

Favorable Safety

e17592 Background: Ra-223, a targeted alpha therapy, showed an overall survival (OS) benefit and favorable safety profile in mCRPC pts in a phase 3 trial. 177Lu-PSMA radioligand is an investigational agent for mCRPC. REASSURE (NCT02141438) is a global, prospective, observational study investigating Ra-223 safety in routine clinical practice over 7 years’ follow-up in mCRPC pts. Data from the second prespecified interim analysis (IA) were used to investigate safety and outcomes of pts who received 177Lu-PSMA after Ra-223 therapy. Methods: Data cut-off for the second prespecified IA was March 2019, and included pts who had subsequent 177Lu-PSMA after the last Ra-223 dose. Disease characteristics, adverse events (AEs) after last Ra-223 dose, and OS are described. Results: Of 1465 pts overall, 26 received 177Lu-PSMA subsequent to Ra-223. In this subgroup, pts received multiple anticancer therapies prior to 177Lu-PSMA. 13 pts (50%) received Ra-223 as combination therapy at second line (metastatic setting). Pts received a median of six Ra-223 doses. After Ra-223 treatment ended, 3 pts (12%) had drug-related serious AEs, 9 pts (35%) had grade 3/4 bone marrow suppression-relevant hematologic AEs. Median duration of 177Lu-PSMA treatment was 3.5 months. 19 pts (73%) received 177Lu-PSMA as fourth-line therapy or onwards. OS was 28.0 months from start of Ra-223 and 13.2 months from start of 177Lu-PSMA. Conclusions: In this select population receiving a sequence of multiple lines of therapy with different modes of action, grade 3/4 hematologic AEs after Ra-223 were low. Treatment with subsequent 177Lu-PSMA seems feasible, based on duration of 177Lu-PSMA and survival. Clinical trial information: NCT02141438 . [Table: see text]

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Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5002 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5002-5002

Author(s):

Silke Gillessen ◽

Ananya Choudhury ◽

Alejo Rodriguez-Vida ◽

Franco Nole ◽

Enrique Gallardo Diaz ◽

...

Keyword(s):

Prostate Cancer ◽

Safety Analysis ◽

Phase Iii ◽

Fracture Rate ◽

Castration Resistant Prostate Cancer ◽

Continuous Administration ◽

Castration Resistant ◽

Radium 223 ◽

Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

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