LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Karim Fizazi ◽  
Namphuong Tran ◽  
Luis Enrique Fein ◽  
Nobuaki Matsubara ◽  
Alfredo Rodríguez Antolín ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Intervention ◽  
High Risk ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points

LBA3 Background: Pts with newly diagnosed mHNPC, particularly with high-risk characteristics, have a poor prognosis. ADT+docetaxel showed improved outcomes in mHNPC, but many pts are not candidates for docetaxel and may benefit from alternative therapy. AA+P is indicated for metastatic castration-resistant prostate cancer pts. LATITUDE evaluates clinical benefit of early intervention with AA+P added to ADT in newly diagnosed, high-risk mHNPC pts. Methods: 1199 pts with newly diagnosed (≤ 3 mos prior to randomization) mHNPC (ECOG PS 0-2) with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) were randomized 1:1 to ADT+AA (1 g QD) + P (5 mg QD) or ADT+PBOs of AA and P. Co-primary end points were overall survival (OS) and radiographic progression-free survival (rPFS). One rPFS (~565 events), 2 interim, and 1 final OS analyses (~426, ~554, and ~852 events) were planned. Results: At this first interim analysis (median follow-up of 30.4 mos; 406 deaths [48%]; 593 rPFS events), OS, rPFS, and all secondary end points significantly favored ADT+AA+P (Table). The IDMC unanimously recommended unblinding the study and crossing pts to ADT+AA+P. Grade 3/4 adverse events (ADT+AA+P vs ADT+PBOs) (%): hypertension (20.3 vs 10.0); hypokalemia (10.4 vs 1.3); increased ALT (5.5 vs 1.3) or AST (4.4 vs 1.5). Conclusions: Early use of AA+P added to ADT in pts with high-risk mHNPC yielded significantly improved OS, rPFS, and all secondary end points vs ADT+PBOs alone. ADT+AA+P had a favorable risk/benefit ratio and supports early intervention with AA+P in newly diagnosed, high-risk mHNPC. Clinical trial information: NCT01715285. [Table: see text]

Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (P) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC): Subgroup analysis of LATITUDE trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 286-286
Author(s):  
Satoshi Fukasawa ◽  
Hiroyoshi Suzuki ◽  
Fuminori Sato ◽  
Katsuyoshi Hashine ◽  
Hisashi Hasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Group Versus ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind

286 Background: Patients with high-risk mHNPC have a poor prognosis. In Japan, mHNPC accounts for approximately 10% of newly diagnosed prostate cancers. AAP was approved for the treatment of castration-resistant prostate cancer in Japan in July 2014. We now report the clinical benefit of AAP with ADT in Japanese patients with newly diagnosed, high-risk mHNPC. Methods: Interim analysis of the multinational, randomized, double-blind, placebo-controlled, phase 3 study, LATITUDE, was previously reported at ASCO2017. We evaluated the superiority of AA 1g + P 5 mg + ADT (AAP group) to ADT+PBOs of AA and P (P group) in mHNPC with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) for the subgroup of Japanese patients. Results: Of 1199 total patients in LATITUDE trial, 70 patients were Japanese (AAP group, n = 35; P group, n = 35). The hazard ratio (HR) for overall survival in the AAP group versus the P group was 0.635 (95% confidence interval [CI], 0.152 to 2.659) and HR for radiographic progression-free survival was 0.219 (95%CI, 0.086 to 0.560). The incidence of adverse events (AE) was 97% (34/35) in both groups. AEs that occurred in the AAP group at a frequency ≥10% compared with the P group included hypertension, hypokalemia, rib fracture, hematuria and hyperbilirubinemia. The incidence of Grade 3 and 4 AEs was 66% in the AAP group and 20% in the P group. As a whole, efficacy and safety of Japanese patients in LATITUDE were shown to be consistent with those of overall population. Conclusions: AAP has shown a favorable risk/benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk prognostic factors. Clinical trial information: NCT01715285.

Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer

2013 ◽  
Vol 31 (14) ◽  
pp. 1740-1747 ◽  
Author(s):  
Karim Fizazi ◽  
Celestia S. Higano ◽  
Joel B. Nelson ◽  
Martin Gleave ◽  
Kurt Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points ◽  
Castration Resistant ◽  
Endothelin A

PurposeAs part of the ENTHUSE (Endothelin A Use) program, the efficacy and safety of zibotentan (ZD4054), an oral specific endothelin A receptor antagonist, has been investigated in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (CRPC).Patients and MethodsIn this randomized, double-blind, placebo-controlled, phase III study, patients received intravenous docetaxel 75 mg/m2on day 1 of 21-day cycles plus oral zibotentan 10 mg or placebo once daily. The primary end point was overall survival (OS). Secondary end points included time to pain and prostate-specific antigen (PSA) progression, pain and PSA response, progression-free survival, health-related quality of life, and safety.ResultsA total of 1,052 patients received study treatment (docetaxel-zibotentan, n = 524; docetaxel-placebo, n = 528). At the time of data cutoff, there had been 277 and 280 deaths, respectively. There was no difference in OS for patients receiving docetaxel-zibotentan compared with those receiving docetaxel-placebo (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P = .963). No significant differences were observed on secondary end points, including time to pain progression (median 9.3 v 10.0 months, respectively) or pain response (odds ratio, 0.84; 95% CI, 0.61 to 1.16; P = .283). The median time to death was 20.0 and 19.2 months for the zibotentan and placebo groups, respectively. The most commonly reported adverse events in zibotentan-treated patients were peripheral edema (52.7%), diarrhea (35.4%), alopecia (33.9%), and nausea (33.3%).ConclusionDocetaxel plus zibotentan 10 mg/d did not result in a significant improvement in OS compared with docetaxel plus placebo in patients with metastatic CRPC.

Personalized peptide vaccination for castration-resistant prostate cancer progressing after docetaxel chemotherapy: A randomized, double-blind, placebo-controlled, phase III trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5033-5033 ◽  
Author(s):  
Masanori Noguchi ◽  
Kiyohide Fujimoto ◽  
Gaku Arai ◽  
Hiroji Uemura ◽  
Katsuyoshi Hashine ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Peptide Vaccination ◽  
Double Blind ◽  
Castration Resistant ◽  
New Treatment ◽  
Docetaxel Chemotherapy

5033 Background: To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA) -A24 positive patients with castration-resistant prostate cancer (CRPC) who failed docetaxel chemotherapy. Methods: Patients were randomly assigned in a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected 6 doses weekly followed the maximum of 30 doses bi-weekly until disease progression. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS) and immune responses. Results: From August 2013 to April 2016, 310 patients were randomly assigned (207 to PPV and 103 to placebo), and 306 patients were analyzed by the full analysis set (204 to PPV and 102 to placebo). Baseline characteristics were balanced between groups. Estimated median OS was 16.1 months (95% CI, 13 to 18.2) with PPV and 16.9 months (95% CI, 13.1 to 20.4) with placebo (HR, 1.04; 95%CI, 0.79 to 1.37; P = 0.77). Median PFS was also not significantly different among them. Median Grade ≥ 3 adverse events were observed in 41% in both groups. The analysis of treatment arm effects among various subgroups revealed a lower HR for OS in favor of the PPV arm in patients with a < 64% neutrophil proportion (HR, 0.55; 95%CI, 0.33 to 0.93), with a significant interaction test ( P = 0.003). Conclusions: PPV did not prolong either OS or PFS in HLA-A24 positive patients with CRPC progressing after docetaxel chemotherapy. Clinical trial information: 0000113088.

Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Arnauld Villers ◽  
Arun Azad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5097-TPS5097 ◽  
Author(s):  
Karim Fizazi ◽  
Julie S. Larsen ◽  
Shannon Matheny ◽  
Arturo Molina ◽  
Jinhui Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Localized Prostate Cancer ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Androgen Synthesis

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.

Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial

2016 ◽  
Vol 34 (18) ◽  
pp. 2098-2106 ◽  
Author(s):  
David F. Penson ◽  
Andrew J. Armstrong ◽  
Raoul Concepcion ◽  
Neeraj Agarwal ◽  
Carl Olsson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Beneficial Effects ◽  
Castration Resistant

Purpose Enzalutamide, a potent oral androgen receptor inhibitor, improves survival in men with metastatic castration-resistant prostate cancer (CRPC) before and after chemotherapy. Bicalutamide, a nonsteroidal antiandrogen, is widely used to treat men with nonmetastatic or metastatic CRPC. The efficacy and safety of these drugs were compared in this randomized, double-blind, phase II study of men with CRPC. Patients and Methods A total of 396 men with nonmetastatic (n = 139) or metastatic (n = 257) CRPC were randomly assigned to enzalutamide 160 mg per day (n = 198) or bicalutamide 50 mg per day (n = 198). Androgen deprivation therapy was continued in both arms. The primary end point was progression-free survival (PFS). Results Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (hazard ratio [HR], 0.24; 95% CI, 0.18 to 0.32; P < .001). Median PFS was 19.4 months with enzalutamide versus 5.7 months with bicalutamide. Enzalutamide resulted in significant improvements in all key secondary end points: time to prostate-specific antigen progression (HR, 0.19; 95% CI, 0.14 to 0.26; P < .001); proportion of patients with a ≥ 50% prostate-specific antigen response (81% v 31%; P < .001); and radiographic PFS in metastatic patients (HR, 0.32; 95% CI, 0.21 to 0.50; P < .001). Beneficial effects with enzalutamide were observed in both nonmetastatic and metastatic subgroups. The observed adverse event profile was consistent with that from phase III enzalutamide trials. Conclusion Enzalutamide significantly reduced risk of prostate cancer progression or death compared with bicalutamide in patients with nonmetastatic or metastatic CRPC.

LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Karim Fizazi ◽  
Namphuong Tran ◽  
Luis Enrique Fein ◽  
Nobuaki Matsubara ◽  
Alfredo Rodríguez Antolín ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Randomized Trial ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Double Blind ◽  
Daily News ◽  
Online Supplement ◽  
Final Text

LBA3 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, June 3, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Tomasz M. Beer ◽  
Eugene D. Kwon ◽  
Charles G. Drake ◽  
Karim Fizazi ◽  
Christopher Logothetis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Phase III study of pembrolizumab (pembro) plus enzalutamide (enza) versus placebo plus enza for metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-641.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS258-TPS258 ◽  
Author(s):  
Julie Nicole Graff ◽  
Joseph Burgents ◽  
Li Wen Liang ◽  
Arnulf Stenzl
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Placebo Treatment ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Points ◽  
Biomarker Analysis ◽  
Receptor Inhibitor

TPS258 Background: The mechanisms of action of pembro, a PD-1 inhibitor, and enza, an androgen receptor inhibitor, may be synergistic in the treatment of patients (pts) with mCRPC. The phase 1b/2 KEYNOTE-365 (NCT02861573) study showed antitumor activity with pembro + enza in pts with mCRPC pretreated with abiraterone acetate. A phase 2 study (NCT02312557) of enza-pretreated patients with mCRPC showed that some pts had a profound and durable anticancer response to pembro + enza. Methods: KEYNOTE-641 (NCT03834493) is a randomized, double-blind, phase 3 trial to evaluate efficacy and safety of pembro + enza versus placebo + enza in pts with mCRPC. An estimated 1200 patients will be randomly assigned 1:1 to receive enza 160 mg/day + pembro 200 mg IV Q3W or enza 160 mg/day + placebo. Treatment will be stratified by prior abiraterone acetate treatment (yes/no), metastases location (bone only/liver/other), and prior docetaxel treatment for metastatic hormone-sensitive prostate cancer (yes/no). Adults (≥18 years) with histologically or cytologically confirmed mCRPC who experienced biochemical or radiographic progression, ECOG PS 0/1, and adequate organ function are eligible. Pts will be required to provide tissue for biomarker analysis. Intolerance to or progression while receiving prior abiraterone acetate therapy is permitted, but not required. Prior chemotherapy for mCRPC, checkpoint inhibition, or any treatment with a second-generation androgen receptor inhibitor is prohibited. Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG3-modified RECIST v1.1 Q9W during the first year and Q12W thereafter. Treatment will continue until progression, unacceptable toxicity, or consent withdrawal, with up to 2 years of pembro/placebo. Dual primary end points are OS and rPFS by blinded independent central review. Secondary end points are time to subsequent anticancer therapy or death, ORR, DOR, PSA response rate, PSA undetectable rate, time to PSA progression, time to pain progression, time to soft tissue progression, time to symptomatic skeletal-related event, and safety. Accrual began July 28, 2019. Clinical trial information: NCT03834493.

Overall survival (OS) analysis of a phase II randomized controlled trial (RCT) of a poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer (mCRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5013-5013
Author(s):  
P. W. Kantoff ◽  
T. Schuetz ◽  
B. A. Blumenstein ◽  
M. M. Glode ◽  
D. Bilhartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Viral Vectors ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Gm Csf

5013 Background: Therapeutic poxviral vaccines for prostate cancer are safe with preliminary evidence of clinical benefit in phase I/II studies. PROSTVAC-VF (PV) comprises 2 recombinant viral vectors (Vaccinia and Fowlpox), each encoding transgenes for prostate specific antigen (PSA) and 3 immune costimulatory molecules (B7.1, ICAM-1, and LFA3: TRICOM). PV is administered subcutaneously in a heterologous prime-boost regimen with concurrent low-dose GM-CSF. Methods: 122 patients (pts) were treated in a multi-center, double-blind, RCT of a vaccination series. Pts were randomized 2:1 to PV + GM-CSF vs. placebo empty vector + control saline injections (C). Vaccinia-based vector was used for priming followed by 6 planned Fowlpox-based vector boosts. The trial completed enrollment in July 2005. Eligible pts had metastatic disease, a rising PSA despite castrate testosterone levels, and a Gleason score of ≤7. Pts with a history of prior chemotherapy use, visceral metastasis, or narcotic use were excluded. The 1º endpoint was progression free survival (PFS), with progression defined as 2 new lesions on bone scan or RECIST-defined progression. Vaccination was discontinued after progression. Results: 82 pts received PV and 40 received C. Pt characteristics were similar (means): age (72PV/76C), PSA (134PV/188C), Alk-Phos (142PV/159C), LDH (207PV/218C), Hgb (13PV/13C), and number bone metastatic sites (5.3PV/6.5C). Mean number of vaccinations was 5.4 PV and 5.3 C. PFS was similar in the 2 groups (p = 0.56). However, at 3 years post study, PV patients had a better overall survival than C patients (25 alive, 30%, PV, versus 7 alive, 17%, C) and a longer median survival (24.5 months PV, versus 16 months C); estimated hazard ratio 0.6 (95% CI 0.4–0.9); stratified log rank p = 0.016. Conclusions: In a RCT, PV immunotherapy was associated with an 8.5 month improvement in median OS in men with mCRPC. These data provide evidence of prolonged anti-tumor activity, but need to be confirmed in a larger phase III study. [Table: see text]

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