A critical review of Provenge. Your inputs welcomed?

[GeorgeGlass]

Any thoughts on this critical review. One thing that strikes me as odd, is how there is no information regarding efficacy since 2012. That's 10 years. If something works well, then why isn't there new data showing that? Some people say, it can't hurt, so just do it. That makes sense if it is true but this review below says that it could shorten lifespan in many, who have weak immune systems. Explains why 90 year olds getting vaccines, frequently don't benefit. I'd like to know that provenge will help with OS but it's odd that there is no conclusive data, if you believe what this review says below. Maybe it's better to just start Nubeqa and skip the provenge?

Any opinions or hard data/facts are welcome.

George

DOI: 10.1093/jnci/djr514 © The Author(s) 2012. Published by Oxford University Press.

Advance Access publication on January 9, 2012. This is an Open Access article distributed under the terms of the Creative Commons Attribution

Non-Commercial License (creativecommons.org/license..., which permits unrestricted

non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sipuleucel-T, an autologous cellular immunotherapy, was approved

in April 2010 by the US Food and Drug Administration (FDA) for

the treatment of patients with castration-resistant prostate cancer.

In July 2010, Kantoff et al. (1) reported the results of the phase III

trial (IMPACT), which was central to the FDA’s approval, and also

underpins the pending application for approval with the European

Medicines Agency. Both the accompanying editorial (2) and the

FDA reviewers noted the lack of supportive evidence for the mechanism proposed by sipuleucel-T’s manufacturer (Figure 1 and

Table 1). The absence of such supportive data has raised the concern that the 4.1-month survival benefit could be the result of a flaw

in the trial design or from the chance imbalance of unmeasured

prognostic variables.

We have reconsidered these trial results in light of unpublished

data obtained from internal FDA documents that became available

only after the approval of sipuleucel-T. We believe that analysis of

the data in their totality challenges the published interpretation of

the trial results and suggests a different conclusion about the efficacy, and potentially safety, of sipuleucel-T. Because these data

have not been debated publicly, we hope that this commentary will

stimulate consideration of their implications.

New Observations From Previously

Unpublished Data

Observation 1: Two Unexpected Interactions Between

Patient Age and Survival

The most striking observation from the new data was an unexpected

11-month difference in median survival between placebo patients

younger than age 65 years and patients older than age 65 years

(28.2 vs 17.2 months, respectively) (Table 2). Age is not normally

prognostic for survival in castration-resistant prostate cancer patients

receiving chemotherapy (7–9), as illustrated by the 17.6-month

median survival for the 504 patients younger than 68 years vs the

18.1-month survival for the 502 patients aged 69 years or older in

the pivotal TAX 327 trial (10). Although post hoc subgroup analyses

should be interpreted with caution, it is still noteworthy that the

age dependence of overall survival (OS) in the placebo arm

(two-sided P < .001) is stronger than the treatment effect itself

(Table 2).

Also, it could be observed for the first time in the unpublished

data from the FDA that among the IMPACT patients younger than

65 years, sipuleucel-T treatment appeared to have no effect on

survival (hazard ratio of death = 1.41, 95% confidence interval = 0.87

to 2.29), in contrast with patients 65 years or older (hazard ratio of

death = 0.58, 95% confidence interval = 0.43 to 0.76) (11). This

observation suggests that the overall results were driven entirely by

the differential survival in older patients. This is counterintuitive

given that standard vaccination strategies (12,13), and immunotherapies in particular (14,15), are consistently less effective in the elderly

and therefore raises further questions concerning the immune

enhancement mechanism proposed for sipuleucel-T. In addition, it

appears remarkable that the younger patients for whom the intervention did not appear to be effective lived longer (median = 29.0

months) than the older patients for whom the intervention did

appear to be effective (median = 23.4 months).

These observations from the unpublished data from the

sipuleucel-T studies generated the hypothesis that the placebo

intervention might have had a clinically significant age-related

impact on OS and should be further investigated to assess whether

COMMENTARY

Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in

Castration-Resistant Prostate Cancer

Marie L. Huber, Laura Haynes, Chris Parker, Peter Iversen

Manuscript received July 11, 2011; revised November 7, 2011; accepted November 16, 2011.

Correspondence to: Marie L. Huber, MPhil, PO Box 925, New York, NY 10009 (e-mail: [e-mail]).

Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic

acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated

by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor

responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the

placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer

patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T

arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival “benefit.” Patient safety depends on adequately addressing this alternative explanation for the trial results.

J Natl Cancer Inst 2012;104:273–279

274 Commentary | JNCI Vol. 104, Issue 4 | February 22, 2012

it might have unintentionally introduced this active non-placebo

effect. In the sipuleucel-T arm, the 5.6-month longer survival of

the younger group, although less statistically significant, is also

unexpected and should be tested against alternative interpretations

of the trial results.

Observation 2: Older Patients in the Placebo Group

Appear to Have Shorter OS Than Might Be Expected From

Other Studies

To test the hypothesis that the placebo intervention had an agedependent effect on OS, we sought placebo groups from other

trials with which their survival might be compared. In the original

publication of the IMPACT trial results, Kantoff et al. (1) state,

“The 21.7-month median survival of patients in the placebo group

compares favorably with that in control groups in other randomized trials involving similar patient populations (range, 15.5 to

21.7 months) (9,16–21), indicating that the treatment effect cannot

be attributed to a poor outcome in the placebo group.” However,

the control groups in the seven cited trials were not appropriate

comparators for the IMPACT placebo group (Table 3). The initial

IMPACT enrollment criteria selected asymptomatic patients with

an Eastern Cooperative Oncology Group performance status of

0 or 1, Gleason score of 7 or lower, and no visceral metastases.

Each of these restrictions is associated with improved OS in multivariable predictive models developed by both Halabi et al. (7) and

Armstrong et al. (8). After 40% of patients had already been

enrolled, the Gleason restriction was removed and minimally

symptomatic patients were accepted. The placebo groups cited by

Kantoff et al. (1) did not share these restrictions and might therefore have been anticipated to have a shorter survival than that of

the IMPACT placebo group. An illustration of how the multiple

enrollment restrictions in IMPACT selected for a favorable prognosis is seen in the 21.2-month Halabi-predicted survival of its

placebo group vs 16 months for the placebo group in the cited

Figure 1. The manufacturing process and proposed mechanism for

sipuleucel-T (3). A) The manufacturing process for sipuleucel-T is

depicted. Mononuclear cells are harvested from the patient and shipped

to the manufacturing facility (approximately 46% T cells, 7% B cells, 13%

natural killer cells, and 25% monocytes) (4) on day 1. On days 2–3, cells

are put through two buoyant density centrifugation steps before incubation for 36–48 hours with a chimeric antigen (PA2024), consisting of

granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate

antigen presentation, which is linked to the prostatic acid phosphatase

(PAP) tumor-associated antigen. Cells are given a final wash on days 3–4

before shipment back to the clinic for reinfusion into the patient. This

process is repeated every 2 weeks for a complete course of three cycles.

B) The proposed mechanism for sipuleucel-T antitumor activity is given.

The manufacturer proposes that during incubation on days 2–3, antigenpresenting cells (APCs) process and present the synthetic antigen

PA2024 on their surface, thereby becoming activated. Upon reinfusion,

these cells are hypothesized to activate endogenous T-cells, thereby

stimulating them to attack PAP-bearing prostate cancer cells.

jnci.oxfordjournals.org JNCI | Commentary 275

Table 1. Areas of concern regarding support for observed survival benefit of sipuleucel-T for castration-resistant prostate cancer*

Concern Public expressions of concern Source

Improvement in overall survival came without

evidence of a measurable antitumor effect

“Study group assignment had no significant effect on the time to tumor

progression.”

(2)

“1 of 341 patients in the sipuleucel-T group had a partial tumor response, and

3% had a reduction of at least 50% in PSA . . .Thus, the improvement in

survival came without evidence of a measurable antitumor effect.”

(2)

“It is hard to understand how the natural history of a cancer can be affected without

some apparent measurable change in the tumor, either evidence of tumor

shrinkage or at least disease stabilization reflected in a delay in tumor progression.”

(2)

Observations predicted by the proposed

mechanism of sipuleucel-T have not been

made. The absence of alternative

mechanisms leaves the 4.1-month survival

benefit without mechanistic underpinning

“It is not clear that Dendreon has put a high priority on measuring the immune

response in patients in their trials. Considering that there appears to be very

little tumor- and antigen-specific immune response in the vaccinated patient,

one would think that this would be a high priority.”

(5)

T-cell proliferative responses to the chimeric

antigen (PA2024) did not translate to

responses to physiologic, human PAP

“The fact that they are able to get a response to PA2024 but consistently

not to PAP tumor antigen is troubling.”

“It was asked if they had any evidence of a specific response to human PAP.

They stated that, no, they do not yet have any evidence.”

(5)

T-cell proliferative response to the

chimeric antigen (PA2024) or human PAP

did not correlate with improved survival

“No survival difference could be detected between patients in the

sipuleucel-T group who had T-cell proliferation responses to PA2024 or

prostatic acid phosphatase at week 6 and those who did not.”

(1)

* PAP = prostatic acid phosphatase; PSA = prostate-specific antigen.

Table 2. Subgroup analysis by age of overall survival of patients

in the phase III trials of sipuleucel-T for castration-resistant

prostate cancer (6)*

Patient

age, y

Sipuleucel-T Placebo

No. of

patients

Median survival

(95% CI), mo

No. of

patients

Median survival

(95% CI), mo

<65 106 29.0 (22.8 to 34.2) 66 28.2 (23.4 to 32.5)

≥65 382 23.4 (22.0 to 27.1) 183 17.3 (13.5 to 21.4)

* CI = confidence interval.

GVAX trial (18). In fact, this predicted 5.2-month survival advantage was not realized because the placebo groups from both of these

two trials lived for a median of 21.7 months.

To find a placebo group with similar baseline characteristics to

those of the IMPACT placebo group, we searched both published

literature and abstracts. We did not find any other castration-resistant

prostate cancer trials with similarly restrictive enrollment criteria.

However, we identified two subanalyses of larger trials that might

provide more appropriate populations to which the IMPACT

placebo group may be compared. 1) In the aforementioned GVAX

trial, Higano et al. (18) reported a subanalysis of the 264 men with

the best baseline prognosis. For men with a Halabi-predicted survival greater than 18 months at enrollment, median survival was

29.7 months on GVAX and 27.1 months in the placebo group.

Because approximately 86% of patients in the IMPACT placebo

group had an Halabi-predicted survival greater than 16 months

(23), the 28.2-month median survival of pooled placebo patients

younger than 65 is in the range that might be anticipated for the

entire IMPACT placebo group. 2) Berthold et al. (24) conducted a

retrospective sub-analysis of the 110 minimally symptomatic patients

from the TAX 327 study; a group similar to, though still not as highly

selected for good prognosis, the IMPACT population. Men with

minimal symptoms had prolonged survival (median = 25.6 months)

compared with symptomatic patients (median = 17.1 months, P = .009).

Furthermore, the median survival for minimally symptomatic

patients in the group given docetaxel every 3 weeks (the chemotherapy regimen received by most of the IMPACT placebo

patients) was 28.4 months. This comparison too suggests that the

28.2-month median survival of the patients younger than 65 years

in the sipuleucel-T trials is in the range of what should have been

expected for all patients, regardless of age.

These comparisons with OS in other CPRC trials support

the hypothesis that the “placebo” intervention might have had a

clinically significant adverse impact on OS in older patients. This

observation too calls for scrutiny of the placebo intervention, to

assess whether it might unintentionally have introduced this effect.

Observation 3: Potential Harm From the IMPACT Study

Interventions

To better understand the potential for harm from the study interventions, we sought data regarding the cellular manipulation in

IMPACT. Kantoff et al. (1) reported no specific cell-level data,

which might be appropriate for a trial investigating the collection

and manipulation of immune cells. Comparison of the cell counts

performed on 526 lots of patient cells received from apheresis centers during an earlier phase III study (9901) (4,25) to the baseline

circulating white blood cell measurements (11) shows that the “standard leukapheresis processing 1.5–2.0 times the patient’s estimated

blood volume” removed more than 90% (median) of the patients’

circulating mononuclear cells. Cells in each lot were counted twice

between steps in the manufacture of sipuleucel-T and underwent a

final count before shipment for reinfusion into patients. Such data

extracted from highly redacted FDA documents revealed that more

276 Commentary | JNCI Vol. 104, Issue 4 | February 22, 2012

Table 3. Comparison of the IMPACT placebo group with placebo groups cited by Kantoff et al. (1)*

Study

No of

patients

Median

OS for

placebo, mo

Reasons why cited placebo group would be

expected to have shorter OS compared with

the IMPACT placebo group Study funding source(s)

Zoledronic acid (16) 208 15.5 The study did not restrict enrollment to minimal or absent

symptomatology. Among patients, 73% had baseline

pain vs 47% in IMPACT. The study conducted before

TAX 327 demonstrated a 2.9-month survival benefit

for docetaxel, leading to its approval by the FDA

in the year 2004

Novartis Pharmaceuticals

Corporation (now Novartis

International AG)

Docetaxel

(TAX 327) (10,17)

335 19.2 The study did not restrict enrollment to minimal or absent

symptomatology, and 45% of patients had clinically

significant baseline pain vs 0% in IMPACT. Baseline

visceral metastases was present in 22% of patients

vs 0% in IMPACT. Clinically significantly worse

baseline performance status and Gleason scores

than IMPACT patients

Aventis (now Sanofi S.A.)

Atrasentan (19) 401 20.3 The study excluded patients requiring opiate analgesia but,

unlike IMPACT, did not enroll 40% of patients under

explicit exclusion of all pain and with favorable Gleason

scores. No eligibility restrictions on patients with visceral

metastases were given. Enrolled from June 2001 to

September 2002, before TAX 327 demonstrated a

2.9-month survival benefit for docetaxel, leading to

its approval by the FDA. The study was conducted

at 180 sites in 21 countries, with variable local

supportive care practices, which could induce bias

in either direction

Abbott Laboratories

ZD4054 phase II (20) 107 17.3 The study excluded patients requiring opiate analgesia,

but unlike IMPACT, did not impose eligibility restrictions

on ECOG status, visceral metastases, pain, and Gleason

score. The study was conducted at 65 centers (of which

only 12 were in North America) across four continents

where placebo patients were given “best supportive

care according to local practice,” which could induce

bias in either direction

Astrazeneca PLC

Mitoxantrone (21) Kantoff et al. (1) chose the arm receiving the low-dose

prednisone (median OS = 19 months) for comparison,

yet the mitoxantrone plus low-dose prednisone

(median OS = 23 months) would represent a more

appropriate comparator for the IMPACT placebo

group in which 50.3% of patients received docetaxel

and 8% received other chemotherapy. The IMPACT

placebo group excluded patients with visceral

metastases [6% of mitoxantrone group in the study

by Berry et al. (21)] and enrolled 75.4% of patients

with favorable Gleason scores. Patients were enrolled

from March 1997 to Jan 1999, and the results were

reported in the year 2001, before docetaxel was granted

FDA approval

Immunex Corporation

Mitoxantrone plus (now Amgen Inc)

prednisone arm

56 23

Prednisone

alone arm

63 19

PROSTVAC

phase II (9)

40 16.6 Post-treatment chemotherapy usage was neither prescribed

nor monitored. Results reported for the 40 placebo

patients are problematic for the many reasons

outlined by Small and Fong (22)

BN Immunotherapeutics

(now Bavarian Nordic)

GVAX (18) ~310† 21.7 Exclusion of opiate pain medication was the only enrollment

criterion used to select for a favorable prognosis

Cell Genesys (now BioSante

Pharmaceuticals Inc)

* FDA = US Food and Drug Administration; OS = overall survival.

† There is an approximate number of participants given for this trial because full results have not been published. The study completed accrual of 626 patients in

the year 2007, randomized 1:1 between study arms, and all patients completed the initial 6-month treatment period.

than 65% (median) of the cells harvested from patients were lost at

the manufacturing facility during the two centrifugation steps

performed on incoming cell lots and during the final cell wash (4).

A more complete description of the sipuleucel-T intervention

would therefore include the extraction of more than 90% of circulating mononuclear cells followed by the return of less than 35%

of these cells 2 days later after incubation with chimeric antigen.

This intervention is repeated three times at 2-week intervals.

Of particular note, the interventions administered to the placebo

group differed from those in the sipuleucel-T group in three

jnci.oxfordjournals.org JNCI | Commentary 277

Box 1. Select aged-related impairments of the immune

system

Decreased thymic production of naive T cells (27,28)

Collapse in diversity of both naïve and memory T cell subcompartments (13,29,30)

Decreased T-cell responsiveness resulting from both decreased

expression of CD28 and proliferative exhaustion (14,31,32)

Increased numbers of circulating natural killer cells with

reduced responsiveness and cytotoxicity per cell (33)

Impaired differentiation of CD34-positive cells into mature

dendritic cells (34)

Decreased frequency of myeloid peripheral blood dendritic

cells (35)

Disruptions in T-cell/B-cell interactions (36)

Alterations in immune cell trafficking as a consequence of widespread changes in cytokine and chemokine signaling (37–39)

important respects. 1) After the two centrifugations that begin the

manufacturing process, two-thirds of the cells in each placebo lot were

removed and frozen for possible later use, leaving only one-third of

the cells for further processing and reinfusion into placebo patients.

Thus, given the greater than 65% (median) of cells lost in processing

and the further two-thirds removed for freezing, less than 12% of

the original pheresed cell load was left for reinfusion into the placebo

patients. 2) Also, cells processed into sipuleucel-T were incubated

with the granulocyte-macrophage colony-stimulating factor/prostatic

acid phosphatase (GM-CSF/PAP) chimeric protein, whereas cells

processed into placebo were stored in medium containing no

GM-CSF. GM-CSF is a cytokine that functions as a white blood cell

growth factor, and furthermore, may have antitumor activity as a

single agent in prostate cancer (26). 3) Whereas cells being processed

into sipuleucel-T were incubated at 37°C for 36–44 hours, placebo

cells were stored at 2°C–8°C. In our experience, storage of isolated

mononuclear cells at 2°C–8°C for 36–44 hours can result in the death

of most, if not all, of those cells. Neither the article by Kantoff et al.

(1) nor the FDA review documents for sipuleucel-T specify a determination of the viability of placebo cells before reinfusion into the

patient. Thus, at best, at each of the three interventions, placebo

patients received less than 12% of their harvested cells back; and at

worst, they received an infusion with an equivalent number of dead

cells. These three differences between the placebo and experimental

interventions were assumed to be benign and have no impact on OS

in this population. However, this assumption remains to be proven,

and the term “placebo” is inappropriate. The IMPACT placebo constituted a biologically significantly different intervention that could

have had distinct clinical properties and was therefore an inappropriate control for sipuleucel-T.

Synthesis and Discussion of Observations

The observations above suggest a simple, albeit unproven, alternative explanation of the IMPACT trial outcome. According to this

alternative explanation, the enrollment criteria selected for a patient

population with a favorable prognosis of approximately 28–29

months and the placebo intervention, involving a repeated depletion of circulating mononuclear cells, exerted an age-dependent

adverse impact on OS. There are several possible explanations for

this. Most simply, patients younger than 65 years may have been

able to replace the lost cells (and clear the dead cells) with few or

no negative consequences, as reflected in their 28.2-month survival

(6). However, patients older than 65 years may have been harmed

by the cell loss (or the infusion of dead cells), as reflected in their

17.3-month survival, which is 11 months shorter than might have

been predicted without the placebo intervention. It is noteworthy

that the sipuleucel-T intervention, involving a similar, though

smaller, repeated depletion of circulating lymphocytes, may have

resulted in a similar, but less severe, age-dependent impact on survival. Although the patients younger than age 65 lived 29 months, the

survival time expected of the entire group, the cells lost during sipuleucel-T manufacture may have contributed to the 5.6-month shorter

survival of patients older than 65 years. Such an explanation would not

involve a therapeutic benefit related to the chimeric antigen.

The field of immunosenescence provides support for this

alternative explanation. The age-dependent deterioration of

multiple components of the immune system are widely accepted

and believed to contribute to the increased incidence of cancer in

the elderly (Box 1) (40,41). Each of these affected elements is

believed to be involved in the recognition and suppression of developing malignancies (42–45), and therefore a depletion of cellular elements by apheresis with inadequate replacement could

exacerbate some or all of these age-related immunodeficiencies.

Because T cells are proposed to be enacting the purported

treatment effect of sipuleucel-T, it is of particular note that the

age-related decline in both naive and memory T-cell diversity is

not linear, but that age 65–70 years is associated with a precipitous

contraction (29,46). This collapse in both number and diversity

of circulating naive T-cells is believed to underlie the poor

response to vaccination in elderly humans and primates

(13,14,47) and by similar mechanisms leads to a reduced ability

to respond to new tumor antigens (14,15). Thus, there is a solid

scientific and mechanistic basis for belief that the interventionrelated depletion could have a greater detrimental effect on the

anticancer immune competence of older individuals, with 65

years representing an important threshold age. Homeostatic

proliferation and migration of peripheral T-cells might maintain

the absolute numbers in the circulation (48); yet the resultant

population would differ from the unperturbed population in

important functional ways (49).

Overall, we believe that a detrimental effect of the placebo intervention is at least as plausible as a beneficial effect of sipuleucel-T

as an explanation of the survival difference observed in the

IMPACT trial. We would be interested in other possible explanations for the 11-month survival difference between placebo

patients older and younger than age 65, as well as explanations for

why the patients in whom sipuleucel-T is apparently efficacious

(aged >65 years) live clinically and statistically significantly shorter

lives than the patients in whom it has no apparent efficacy (aged <65

years). The safety of prostate cancer patients as well as the

278 Commentary | JNCI Vol. 104, Issue 4 | February 22, 2012

judicious development of beneficial immunotherapies depends

on addressing the concerns raised and considering all possible

interpretations of the IMPACT trial results.

References

[cesces]

No one here talks about provenge much either.

That would mean not many people are being treated with it.

[Seasid]

My MO doesn't recommend Provenge because it doesn't lower the PSA.

Would be ok if I organize it for myself, but I simply don't have enough money to do Provange.

The Chinese are owners on the paper.

Everything is in the USA therefore nothing to do with the Chinese exept the ownership on the paper.

I would gladly take Provange with SBRT or with chemotherapy.

[Yank66]

can’t site the study, but MO said Provenge extended survival by 2 years and not to evaluate it’s success by PSA

[GeorgeGlass in reply to Yank66]

thanks yank. See if you can get that study info from your MO. It would help inform all the guys on here.

[GeorgeGlass in reply to Yank66]

maybe this: healthunlocked.com/redirect...

[Yank66 in reply to GeorgeGlass]

Maybe that's the one- MO said 2 years and this study says 14+ months. Haven't seen him to ask since before this thread. (Didn't want you to think I was ignoring you)

[GeorgeGlass in reply to Yank66]

Paul, (Mateo) provided the link. It can maybe be due to people being more proactive, who get provenge but it seems like the potential benefit outweighs the costs.

[pjd55d]

I did Provenge ( 3 treatments 2 weeks apart ) in 2018. My Mets have shrunk and become les dense and my PSA has stayed down ( also on Eligard every 3 months ) My Oncologist feels that the Provenge has contributed in a positive way.

I am not knowledgeable or able to get into any kind of discussion quoting chapter and vers of the treatment.

I AM calling it a plus for me and grateful for the treatment

Best

[GeorgeGlass in reply to pjd55d]

thanks PJ. That’s good news. Could the improvement been due to anything else, like adt? Or was Provenge the only thing you did differently before the tumors improved?

[MateoBeach]

You copied the full text on that one George.

But you perhaps didn’t see this from 2019. Real world results from Provenge

urotoday.com/recent-abstrac...

[GeorgeGlass in reply to MateoBeach]

thanks Paul. This Is a positive piece. It sounds promising that it’s a good medium term benefit. There’s no long term comparisons because it’s too new. That’s the case with most 2nd line and crpc treatments. We have to make an informed guess what we want to try.

I think Medicare claim related results are a good way to compare effectiveness. What are they referring to when they say “oral agents”? What are the names of some oral agents that they compared to Provenge?

Sorry about my long cut and paste entry. I couldn’t find a way to make my pdf into a link.

[Union98]

Keith believes Provenge has helped him. Diagnosed in December 2016, Gleason 4+3, 3 bone mets, lots of lymph nodes involvement, PSA 43. Started ADT (Casodex/Lupron), 6 rounds of taxotere, started Zytiga Dec 2017. Provenge in 2019. He decided to take a Zytiga/abiraterone break and PSA has continued to be undetectable for 6 months (ongoing Lupron). He does yearly scans and next scan is due in the spring.

[GeorgeGlass in reply to Union98]

excellent news! I wish continued success. I'm working on the provenge approval.

[GeorgeGlass]

healthunlocked.com/redirect...

[GeorgeGlass]

i can’t answer any of those things. I don’t know why any of the pharmaceutical companies do anything other than to make as much money as possible. None of them do anything with all the nih research showing promise in natural treatments.

The link i sent shows the Provenge treated guys do better. Maybe that’s due to those people being more proactive out maybe it’s because sone guys get an immune boost that helps the body to resist tumor development in the bones or something. People on this website analyze things more than the medical and pharmaceutical community seem to do, much of the time.