white senior man driving a golf cart

Prolonged Survival

PROVENGE:

Powerful overall survival data

IMPACT: PROVENGE has been clinically proven to extend life for certain men with mCRPC.

In IMPACT, the double-blind, placebo-controlled trial that supported FDA approval of PROVENGE, men with mCRPC (N=512) were randomly assigned in a 2:1 ratio to receive either sipuleucel-T (n=341) or placebo (n=171). The primary endpoint was overall survival. Men who received the immunotherapy experienced a significant overall survival advantage.3

a Hazard ratio and P value based on the Cox proportional hazards model adjusted for PSA (ln) and LDH (ln) and stratified by bisphosphonate use, number of bone metastases, and primary Gleason score.
CI confidence interval; LDH, lactate dehydrogenase; ln, logarithm; PSA, prostate-specific antigen; mCRPC, metastatic castration-resistant prostate cancer.
Summary of Overall Survival Results3
PROVENGE
(n=341)
Control
(n=171)
Overall Survival Median, months (95% CI)25.8
(22.8, 27.7)
21.7
(17.7, 23.8)
Hazard Ratio (95% CI)0.775a
(0.614, 0.979)
P value0.032a

Nearly 38% more men who received PROVENGE were still alive 3 years post treatment compared to control.1,b

b This information is data on file and represents an unpublished exploratory analysis.
IMPACT: Percentage of Patients Alive—ITT Population (95% CI)1,b
1 Year2 Years3 Years4 Years
PROVENGE81.1% (76.9, 85.3)
n=274
52.1% (46.4, 57.7)
n=129
31.7% (25.7, 37.8)
n=49
20.5% (14.0, 26.9)
n=14
Control72.4% (65.6, 79.1)
n=123
41.2% (33.5, 49.0)
n=55
23.0% (15.5, 30.5)
n=19
16.0% (8.5, 23.4)
n=4
ITT, intent to treat.

IMPACT data suggest longer overall survival benefits for men who start PROVENGE with a lower PSA level2,c

Data from the exploratory analysis suggest that men with a baseline PSA of ≤22.1 ng/mL, when treated with PROVENGE, lived more than 1 year longer than men who did not receive PROVENGE (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.31-0.85).2,c

c This post hoc analysis was not powered for statistical significance, and the population within the subgroups was not randomized. Therefore, the findings are limited by their exploratory nature.

Tell me about IMPACT

PROVENGE delivered a statistically significant median overall survival advantage in clinical trials1,3

line graph

In an open-label salvage protocol, upon progression, 64% of control group patients elected to cross over to APC8015F, a product manufactured according to the same specifications as sipuleucel-T but from cells cryopreserved at the time the placebo was prepared, upon progression.3

A prolonged immune response shown in the IMPACT trial9

A sustained immune response of up to 26 weeks (the last time point measured) was observed in men who received PROVENGE in IMPACT.9,e

d Individual results may vary.
e No conclusions could be made regarding the clinical significance of the observed immune responses.
26 weeks

Real World Observations

The Medicare beneficiary study of PROVENGE

A retrospective observational analysis of the Medicare fee-for-service 100% dataset was examined to evaluate the effect of PROVENGE and the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate and enzalutamide on overall survival (OS) in men treated for advanced prostate cancer. The study identified 6044 men with a prostate cancer diagnosis who received either PROVENGE or ASPIs in 2014. These men were then observed during the 3-year period from 2014-2017 or until death.4

This study measured outcomes for 2 analysis cohorts.

Any-line cohort:

Examined any-line treatment with PROVENGE and any-line treatment with ASPIs but not PROVENGE.f

First-line cohort:

Examined first-line treatment with PROVENGE and first-line treatment with an ASPI but not PROVENGE.


bar graph for any-line treatment
At 36 months

Median OS in men receiving PROVENGE in any-line of treatment was 14.5 months longer than for those receiving ASPIs in any line of treatment (but not PROVENGE).

f Men in the any-line cohort could have received any other agent during the observation period except for those in the ASPI group who by definition did not receive PROVENGE.

bar graph for first line treatment
At 36 months

Median OS was nearly 14 months longer in men receiving PROVENGE in the first line of treatment than in those receiving an ASPI in the first line.


The study analysis suggests that the use of PROVENGE at any time was associated with improved OS compared with ASPI use alone.

Claims analyses like these are limited in their ability to reliably predict treatment effects, and individual results may vary. This claims dataset does not include safety or certain clinical assessments; the analysis was exploratory and the results need careful interpretation.

The PROCEED Registry

PROCEED is the largest real-world registry to evaluate the safety and survival profile of PROVENGE in men with asymptomatic or minimally symptomatic mCRPC. The registry, which was conducted between 2011 and 2017, enrolled nearly 2000 men who received PROVENGE in an everyday treatment setting.5

This subgroup analysis of the PROCEED registry was exploratory and results need careful interpretation.


pie chart for treatment for 1 year

PROCEED evaluated the safety and survival profile of PROVENGE. Among patients in the lowest baseline prostate-specific antigen (PSA) quartile (≤5.27 ng/mL), nearly half (44.1%) of the men in the registry received no additional cancer treatments for at least 1 year. Of these men, nearly 95% received PROVENGE (sipuleucel-T) as a first-line treatment.5


In a post hoc analysis of the PROCEED registry, median overall survival was greater in men who started PROVENGE with a lower baseline PSA level6,g

For men whose PSA was ≤5.27 ng/mL: Median overall survival was nearly 4 years from the time of treatment selection5

g The PROCEED registry evaluated the safety and survival profile of the PROVENGE received by patients in a real-world setting in which there was no control group. The study was conducted to quantify the risk of cerebrovascular event and survival. Patients may have received subsequent anti-cancer interventions, per the local investigator's standard of care.
h this subgroup analysis of the PROCEED registry was exploratory and results need careful interpretation.

SIPULEUCEL-T (PROVENGE) IS RECOMMENDED BY NATIONALLY RECOGNIZED ORGANIZATIONS

AUA logo

AUA recommends sipuleucel-T (PROVENGE)7

In men with mCRPC who are asymptomatic or minimally symptomatic, clinicians may offer sipuleucel-T. In sequencing agents, clinicians should consider prior treatment and consider recommending therapy with an alternative mechanism of action (Evidence Level: Grade B).

sitc logo

SITC recommends sipuleucel-T (PROVENGE)8

The current evidence-based recommendation for the use of sipuleucel-T (PROVENGE) in the management of mCRPC in asymptomatic or minimally symptomatic patients is supported by Level A evidence from randomized trials and meta-analyses. Sipuleucel-T (PROVENGE) may achieve greater benefit among mCPRC patients treated earlier in the course of the disease.

References
1 Data on file. Dendreon Pharmaceuticals LLC.
2 Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology. 2013;81(6):1297-1302. doi:10.1016/j.urology.2013.01.061
3 PROVENGE [prescribing information]. Seal Beach, CA: Dendreon Pharmaceuticals LLC; 2017.
4 McKay RR, Hafron JM, Ferro C, et al. A retrospective observational analysis of overall survival with sipuleucel-T in Medicare beneficiaries treated for advanced prostate cancer. Adv Ther. 2020;37(12):4910-4929. doi.org/10.1007/s12325-020-01509-5
5 Higano CS, Armstrong AJ, Sartor AO, et al. Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Cancer. 2019;125(23):4172-4180. doi:10.1002/cncr.32445
6 Sartor O, Armstrong AJ, Ahaghotu C, et al. Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry. Prostate Cancer Prostatic Dis. 2020;23(3):517-526. doi:10.1038/s41391-020-0213-7
7 Cookson MS, Roth BJ, Dahm P, et al. Castration-resistant prostate cancer: AUA guideline. J Urol. 2013;190(2):429-438. doi:10.1016/j.juro.2013.05.005
8 McNeel DG, Bander NH, Beer TM, et al. The Society for Immunotherapy of Cancer consensus statement on immmunotherapy for the treatment of prostate carcinoma. J Immunother Cancer. 2016;4:92. doi:10.1186/s40425-016-0198-x
9 Sheikh NA, Petrylak D, Kantoff PW, etc. Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunology Immunotherapy. 2013;62: 137-147. DOI: 10.1007/s00262-012-1317-2.
INDICATION

PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION

Acute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.

Full Prescribing Information.

To report an adverse event, please email our Pharmacovigilance department at drugsafety@dendreon.com, or fax adverse event details to 833-464-0123. Please provide details pertaining to the adverse event and provide contact information so that our Pharmacovigilance team may contact you with any questions.
To report a product complaint, email our Quality department at CQAcomplaints@dendreon.com. Please provide details pertaining to the quality issue and provide contact information so that our Quality team may contact you with any questions.
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