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LOS ANGELES, March 3 (Reuters) - Updated trial results show that an experimental cancer vaccine developed by Dendreon Corp improved three-year survival of patients with advanced prostate cancer by 40 percent compared with a placebo.
03/03/2010
* Provenge extends 3-yr survival by 40 pct vs placebo
The results, based on 36.5 months of follow-up, confirm earlier 34-month data presented last year, which showed that the drug improved survival by 38 percent.
Patients in the 512-patient study who received Dendreon’s Provenge lived an average of 4.1 months longer than those who were given a placebo, according to the latest tally announced by the company on Wednesday.
Unlike traditional vaccines that prevent disease, Provenge treats it by stimulating the body’s own immune system to attack cancer cells. It is produced by taking cells from a patient’s tumor, incorporating them into a vaccine, then returning them to a physician to be injected back into the patient.
CEO Mitchell Gold: “met its pre specified end points” “confirms results of previous studies” “data met criteria and specifications of Biologics License Application” “results were robust” “results were unambiguous and held up to multiple sensitivity analysis” “a clear hit on statistical significance.”
“It is the first active immunotherapy to show a survival benefit in a phase 3 study. It is a tremendous accomplishment for the company and it means a tremendous amount for prostate cancer patients across the world. ”
“We showed a survival benefit, which is the gold standard outcome of oncology clinical trials, in a large randomized phase 3 trial.”
Dendreon Home Page >> http://www.dendreon.com/
Dendreon News http://investor.dendreon.com/releases.cfm?header=news
May 14, 2009
Dendreon Corporation CEO Mitchell H. Gold, M.D. Named Ernst & Young Entrepreneur Of The Year® 2009 Award Finalist in the Pacific Northwest
Apr 28, 2009
Dendreon Presents Preclinical Data Demonstrating Activity of TRPM8 agonist, D-3263, in Benign Prostatic Hyperplasia
Apr 21, 2009
Dendreon Initiates Phase 1 Clinical Trial of Small Molecule Targeting TRPM8 in Cancer
Apr 19, 2009
Dendreon Announces Data on PROVENGE Potency and Long-Term Immune Responses in Androgen-Dependent Prostate Cancer
Apr 14, 2009
PROVENGE Significantly Prolongs Survival in Men with Advanced Prostate Cancer in Pivotal Phase 3 IMPACT Study
Dendreon Pipeline>> http://www.dendreon.com/pipeline/
PROMISING NEW CANCER THERAPIES ON THE HORIZON
Dendreon is focused on discovering, developing and commercializing novel therapeutics to fight cancer. Our pipeline includes active cellular immunotherapy, monoclonal antibody and small molecule product candidates to treat a wide range of cancers.
The dedication of our research and development team has resulted in our lead product candidate, sipuleucel-T, rapidly approaching commercialization.
Sipuleucel-T, an active cellular immunotherapy, is in late-stage development for the treatment of metastatic, androgen-independent prostate cancer.
Lapuleucel-T, an active cellular immunotherapy, is in development for breast, ovarian and colon cancer.
CEA, an active cellular immunotherapy, is in preclinical development for breast, lung and colon cancer.
CA-9, an active cellular immunotherapy, is in preclinical development for kidney, colon and cervical cancer.
Trp-p8 (also known as Trp-M8), a small molecule, is in preclinical development for prostate cancer.
Dendreon Therapeutic Approaches >> http://www.dendreon.com/therapeutic_approaches/
Link to >> Froggmisters Dendreon Research Blog
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Information prior to achieving statistical significance
There was ample of evidence of survival benefit conferred by Provenge as a treatment in contrast to Dr. Pazdur’s statement: “Believe me, if there were a clear survival effect, the drug would be approved,”. In fact, Dr. Pazdur’s focus on the statistical flaws showed that the main problem in the FDA drug approval process as practiced by Dr. Pazdur is a slavish following of rigid statistical rules without properly factoring in clinical knowledge required to give meaning to such numerical data.
The irony is that FDA has a process to incorporate clinical knowledge into drug evaluation. Advisory Committees made up of world-class experts are often convened to discuss clinical data and provide advices to the FDA during the evaluation of drugs up for approval. The AC convened to consider Provenge voted 17-0 that the drug was safe and 13-4 that there was substantial evidence that it was effective. When Dr. Pazdur helped rejecting Provenge, he effectively ignored that body of knowledge. He showed himself to be not only a slave to simple statistical calculations but also one who cared little for the scientific process and the needs of desperate patients.
The FDA’s initial excuse was that it missed on Time To Progression (TTP) by 2 one thousandths of one percent. It showed increased survival but since the FDA told them to have TTP as the primary endpoint they would not approve on a secondary endpoint of survival. They asked for more efficacy evidence and essentially agreed there were no safety issues.
At an interim peek at the IMPACT trial results in October 2008, Provenge showed survival consistent with its previous studies. Provenge works like a vaccine and takes time to ramp up (the trial was not designed to show optimal additional survival at the interim peek as the survival curves have previously been demonstrated to separate later in the trial).
Still Provenge showed additional 20% survival for late stage patients in the Provenge arm at the early look. The FDA said the additional 20% survival evidence is still not enough….. we need to see 22%. So the trial continues and Provenge is destined to sit on the shelf being denied access to the patients for another 1-2 years. It has already been delayed over a year and a half.
A .002 miss, and a 2% miss and its not good enough for a patient class who are AIPC or HRPC and have no good treatment options?
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For Provenge, the clinical data were:
- D9901, a phase 3 trial enrolling 127 patients, whose primary endpoint, Time To Progression, barely missed statistical significance with p-value .052 and Overall Survival was highly significant with p-value .01. The survival rates at three years were 1 in 3 for patients treated with Provenge compared to 1 in 9 for patients treated with placebo. Per several sensitivity analysis performed by the FDA statisticians themselves, this trial was well run, the data self-consistent and the survival benefit unlikely to be spurious.
- D9902a, a smaller phase 3 trial enrolling 98 patients, missed statistical significance for both TTP and OS. Again, per analysis done by FDA statisticians, this trial unfortunately enrolled much sicker patients on the treatment arm than on the control arm. This imbalance meant that patients on the treatment arm died faster without any intervention and that stipulated the miss of statistical significance. However, after three years, even with such a disadvantage, Provenge stopped the disease in time to again save 1 in 3 patients on the treatment arm compared to 1 in 5 on the placebo arm.
- The Hazard Ratio is a common measure of comparative risks of death between two treatments. The D9901 trial exhibited an HR of 0.58 meaning that patients on the treatment arm had 42% survival advantage over patients on the placebo arm. The D9902a trial exhibited an HR of 0.76 or a 24% survival advantage for treated patients.
- Patients in D9902a were much sicker than D9901 and more similar to the patients enrolled in the TAX327 trial that led to the FDA’s approval of the chemotherapy Taxotere as the current Standard Of Care for prostate cancer. The HR for TAX327 was also 0.76 comparable to D9902a.
- Another Taxotere phase 3 trial, SWOG99-16, showed a worse HR of 0.80. At three year, less than 1 in 5 treated patients were still alive. After four years, all passed away. There are patients treated with Provenge still living today after six to seven years.
- Placebo patients in the Provenge trials were allowed to cross over to take a form of Provenge made from their cryo-preserved blood. Of the 12 out of 78 patients on the placebo arms of the Provenge trials D9901 and D9902a who survived past three years, only two did not cross over. The cross-over protocol was there for compassionate reason. But without it, the survival benefit of Provenge over non-treatment would have been much clearer in the statistical sense
7. Provenge Interim Results Transcript Oct. 6, 2008 http://www.investorvillage.com/smbd.asp?mb=971&mn=226726&pt=msg&mid=5911033http://
www.investorvillage.com/smbd.asp?mb=971&mn=226726&pt=msg&mid=5911033
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Provenge Interim CC Oct 6 transcript
This is Jennifer Williams and we are happy you could join us today for our conference call. Joining me are Mitch Gold, Jon Schiffman, David Urdal and Mark Froelich. (disclaimer stuff)…turn over to Dr. Gold:
Gold: Thanks Jennifer…First let me remind you of the design of this study. The IMPACT study is a randomized, double blind, placebo controlled phase 3 study that enrolled 512 men with metastatic, androgen independent prostate cancer.
The primary endpoint of the trial is overall survival. The statistical plan was designed using the integrated results of two previous Phase 3 studies, 9901 and 9902a. The interim analysis was performed by an independent data monitoring committee, or IDMC. The IDMC reported no safety concerns and recommended that the study continue to its final analysis. While we remain blinded to the data, the committee reported to Dendreon a 20% reduction in the risk of death in the Provenge arm relative to placebo, a hazard ratio of .80. Alternatively the hazard ratio can be expressed as 1.25, representing a 25% increase in the risk of death in the placebo arm relative to the Provenge arm. At the final analysis, which is anticipated in the middle of 2009, if the study demonstrates an approximately 22% reduction in the risk of death, based on 304 events, the company would expect the study to meet its primary endpoint of overall survival.
While we would have liked to have received results that would have allowed us to amend our BLA at this time, as we said before, the final analysis is designed for a higher probability of success. Here are a few key considerations as we look forward to the final analysis from IMPACT. At the time of the data cutoff for the interim analysis, which occurred in May of this year, the median follow up time in the IMPACT study was approximately 24 months. As we reported today, we observed a 20% reduction in the risk of death in the Provenge arm with a hazard ratio of .80. Now if we look at the integrated analyses of results from 9901 and 9902a at a similar follow up time of 24 months, we observed a 22% reduction in the risk of death, a hazard ratio of .78. Therefore, these results are consistent with those from our previous completed Phase 3 studies of Provenge in this patient population at a similar follow up time.
As you may recall, the final analysis from our integrated studies showed an approximately 33% reduction in the risk of death, a hazard ratio of .67, supporting the hypothesis that there is a delayed treatment effect of Provenge, which tends to get larger over time. Given that the results reported today are consistent with those from our previous integrated analyses, at a similar follow up time, we are looking forward to the final analysis of the IMPACT study next year.
Prostate cancer is, without question, a difficult disease to treat, with only one product in the past 20 years that has been approved by the FDA that has shown an improvement in overall survival. Before we conclude, I would like to thank the hundreds of men who have participated in the IMPACT study. In the 10+ years that Provenge has been under study for the treatment of advanced prostate cancer, more than 800 men have participated in the clinical studies. These men have demonstrated courage in their participation in our clinical trials, and have contributed to what we hope will be an advancement in medical care for prostate cancer patients. At this time I’ll turn it over to Q and A:
Mark Monane, Needham and Co.: Thank you for reviewing the results with us…the hazard ratio that you reported, is that an adjusted log rank analysis? I remember you talked about adjusting for certain factors and maybe you could go over those factors and answer that question first.
Gold: I’ll let Mark take that one.
Froelich: The analysis was an adjusted Cox model in which we adjust for the prognostic factors PSA and LDH
Monane: OK, that was helpful. And then in the follow up, I guess the question is, in the final analysis will the patients still alive will continue to contribute data points in the trial, patients that are dead will not, but the question is, in the trial recruitment, the patients that were recruited later in this trial study, can you tell me whether these patients were similar to those recruited earlier in the study? Is there any reason to believe those patients would be different?
Gold: What we’ve said in the past, and what we know is that we’ve conducted a Halabi analysis on the total patient population from the IMPACT study and compared to that from 9901 and 9902a and we see that the patient population is very similar to that what we saw in 9901 as well as the integrated analyses. So the Halabi model shows that the baseline characteristics are consistent with what we’ve seen in our other studies.
Monane: When you say with the 22% reduction in risk you’re talking about a Hazard Ratio of .78, is that how we should interpret it?
Gold: That is correct.
Monane: …and at that point when you say meet the primary endpoint outcome you’re saying that that p value would be less than .05 with a Hazard Ratio not eclipsing 1?
Gold: …um, would meet the pre-specified level of fiscal analysis plan for the final analysis…yes.
Monane: OK. Then we can assume that today the date that you reported today did not meet that endpoint…is that a fair assumption?
Gold: Correct. It did not meet the pre-specified criteria to allow us to amend our BLA. That being said what we can take away from the data that we received on the interim analysis is that it is very consistent with what we saw on the integrated analyses of 9901 and 9902a and that both studies have shown an increased benefit over time. I guess another caveat to that is that not only in the integrated analysis but in 9901 and 9902a we saw the treatment effect increase over time.
Monane: Have any patients been lost to follow up…do you have data points on all of the patients going forward?
Gold: Right now its difficult for us to say but there’s been very few patients lost to follow up…it’s not 100% as it was in 9901 but its very close.
Monane: I’ll get back in the queue…thanks for the added information.
Joel Sendek, Lazard Capital Markets: Can you tell us what the P value was at the interim analysis.
Gold: As we said in the past, we keep the details of the fiscal analysis plan and we look at that as proprietary to the company, but what I can tell you is that the final number of events is 304 events, and we’ve preserved a substantial amount of alpha for the final analysis.
Sendek: That was my second question…which is…what is that?
Gold: Let me just emphasize, as Mark just mentioned, the company did not receive a p value from the IDMC for the interim analysis.
Sendek: Can you tell us what the alpha spend is at this point so we’ll know what you’ll need at the final analysis?
Gold: What I can say is that we’ve preserved a substantial amount of the alpha for the final.
Sendek: In the answer to Mark’s question you said that you’d need a .05, so I’d presume that number would be less than .05, right?
Gold: Mark said .05…we never said .05. I think the best way to look at it Joel is to look at the stats, so if we say we need a 22% reduction in risk of death in the final analysis then we would expect to achieve the statistical hurdle.
Sendek: Presumably what you are saying this morning is that you just missed it. If the interim were .78 as opposed to .80 you would have stopped the trial?
Gold: All I can tell you is that we did not meet the pre-specified criteria for stopping and amending our BLA but I see going forward we need a 22% reduction. We’re at 20% today and, historically we’ve seen an increase in the treatment effect over time in our clinical studies so we’re looking forward to the analysis that we’re going to receive next year.
Sendek: Just one more…so if it’s in line with what you thought but you missed the interim, I’m wondering, did you make a mistake when you came up with your interim statistical analysis plan, you know, because there’s a disconnect there in my mind and I’m wondering if you could explain.
Froelich: The study was powered on the final results of the integrated results of 01 and 02a, which was a risk reduction of 33% so the interim result has less power than the final analysis by design so we still feel reasonably comfortable with our projections for the final analysis
Sendek: Thank you.
David Miller, Biotech Stock Research: The interim would have had to have a much lower hazard ratio than .22 to be successful, correct?
Gold: Much is a descriptive term…
Miller: Would have to have a lower than…
Gold: It would have had to have had a lower hazard ratio than we observed today for us to meet the pre-specified criteria for stopping…
Miller: Right, but you said you have to have a 22% risk of death or a .78 Hazard Ratio, that will be sufficient to get success at the final analysis, correct:
Gold: That is correct. Two things to take into consideration. One is the treatment effect, the other is the increased number of events.
Miller: But if you had shown that .78 Hazard Ratio today because of p value spend and things like that that have to do with the interim it would have not have been successful.
Gold: We have not talked about that specifically, i.e. what would we have needed at the interim to be successful but I think we wanted to give, going forward, that if we have a 20% reduction of risk today, and based on how much alpha we’ve preserved for the final we need to meet a 22% reduction of the risk of death.
Miller: I’m going to move on to something else then. Can any of the patients on the control arm roll over now or are they all past that point?
Gold: The patients that are in the control arm can still roll over if they want and the roll over rate to the frozen version of Provenge has been consistent with what we’ve seen in the previous Phase 3 studies.
Miller: The first number of patients into the trial had a lower Gleason score by trial enrollment and you have said that in our previous trials, the previous trials, that the Hazard Ratio improved, can you talk a little bit about how you would respond to the question or to a charge that this data kind of shows the healthier patients, the patients later on the trial, by definition, by Gleason score, were sicker, therefore its unlikely that they would see the same improvement as the trial goes forward.
Gold: What I would emphasize, first off, is that the patient population as a whole in IMPACT is based on Halabi and is very similar to what we saw in 9901. And 2nd what I would point you to…I know you’re familiar with this poster, this poster that Dr. Aaron Small presented at the ASCO Prostate Cancer meeting a couple years back, we showed that biggest percentage differences in survival were in patients with the highest with the highest Gleason scores. So the take home message is that the survival benefit that we’re seeing is independent of Gleason score.
Miller: My last question is…given that there is this clear tail effect, and that the data looks better going forward, the longer out you go, are you worried or do you have any second thoughts about moving that final analysis forward?
Froelich: The final analysis is pre-specified under the protocol to happen at 304 events so we can’t change that at this time but as I noted before we comfortable that the trial was
adequately powered for an overall reduction of 31% which is consistent with what we saw in our prior trials and integrated analysis.
Gold: And David what I’d like to emphasize is, I don’t know if you picked it up in my prepared comments, the data cutoff date for the interim actually occurred in May of this year…
Miller: Yeah, I did pick that up.
Gold: So…
Miller: You guys made an amendment that essentially accelerate that final analysis from sometime in 2010 to I assume it’s still second half of 2009…are we still 2nd half of next year for the final?
Gold: We said middle of next year…
Miller: OK, middle. So you accelerated that from 2010. Given that there is this tail effect are you having 2nd thoughts about doing that?
Gold: No, because I think what we see is that a 20% reduction of risk of death today with a median follow up of 24 months is very similar to what we saw in the previous Phase 3 studies and if that occurred in May and the final is going to occur sometime in the middle then I think we’re pretty comfortable with the…if the treatment effect repeats itself and it tends to increase over time in effect as it did in 9901 and 9902a and the integrated analysis then I think we’re comfortable with that.
Miller: I guess I do have a final question. I just want to make sure that I understood the answer to Mark’s first question…this is the adjusted Cox hazard ratio?
Gold: Correct.
Miller: OK. Thanks. I’ll jump back in queue.
Gold: David? The last thing is that when we gave you the .78 number at 24 months for the integrated analysis that was also on an adjusted Cox basis as well.
Miller: OK, perfect, thank you.
William Ho, BOA: Could you discuss the recent failures of some of the other companies in the area of immunotherapy and what perhaps makes you different and increases you confidence in success next year.
Gold: Without getting into specifics, in general, prostate cancer has been a very difficult disease to treat and we’ve several studies out of late that have shown a negative treatment effect on overall survival. We’re very encouraged by the results that we’ve seen today in the interim analysis showing a 20% reduction in the risk of death. I can’t speculate as to why those studies have failed and we’ve seen the data that we’ve seen today, but I think there are some inherent differences that I should highlight. First, we use a recombinant protein as our antigen delivery cassette, and that recombinant protein technology I do think is a key piece of why we are able to generate a substantial immune response against the antigen delivery cassette. Second, we use an ex-vivo process to load up the dendritic cells and as a result we take it out of the immunosuppressive environment that exists in vivo, within the cancer patient, and are able to activate the dendritic cells and we give a very large number of active antigen presenting cells that comes back to the patient. So I think there’s probably a whole host of factors that may be contributing. I don’t think there is anything that we can conclude right now but I think we’re encourage by the results that we’ve seen today, particularly in light of the results that we’ve seen come out over the last year or so.
Ren Benjamin, Rodman: Can you let me know if a futility analysis was part of this interim analysis, and if so, what would have been required to stop the trial because of futility?
Gold: As we’ve said in the past there was no futility analysis as part of this interim analysis.
Benjamin: The hazard ratios that were reported…was in a different manner than it was presented in the past…was there a reason why there was a switch here?
Gold: There is a lot of debate in scientific literature about what is the best way to report these hazard ratios. The way that we reported it today is one that is becoming an increasing trend in the lit. and we felt it was important to go to that trend as we look forward to publishing this data and having it consistent with what the community is seeing.
Benjamin: Based on the rate that you’re seeing right now is there any chance that your final analysis comes in even earlier than what you’re predicting now?
Gold: As we said in our prepared comments we’re comfortable with projecting out to the middle of 2009.
Aaron Reems, Wachovia: Could you provide us with the confidence interval for the 24 month hazard ratio that you provided us at .78.
Gold: I don’t have than right now Aaron.
Reems: OK. With data cutoff coming in May can you walk us through what needed to occur between data cutoff and now, and was it expected to take 5 months to gather that data for the review or were there other things that were affecting things for the Data Safety and Monitoring Board getting together to review that data?
Froelich: Just to clarify, we had to clear the entire data base, not just the survival but all the safety and other info needed to file a BLA should the interim have been positive. That’s the amount of time, with more than 80 clinical sites, to bring all the data in, clean it, and lock the data base.
Monane: In the previous data set we saw some long survivors…a certain percentage of patients were alive 3 years later…can you tell us anything about that with the new data set?
Gold: No. We’re blinded to the data Mark so we have no additional data on, for example, the shape of the curves or long term survivors, etc.
Monane: How about the standard deviation of the trial? Obviously that’s going to be an important statistical analysis. Can you describe that or tell us if that was consistent with what you saw in the previous 9901 analysis?
Gold: Mark, everything that we received from the IDMC is included in the press release today.
Monane: The company published some information about the role of a booster shot and the utility a trial you did in some Provenge patients. Can you talk about that a little more and did any patients get an opportunity to get a booster? I know it would probably be a frozen booster. Was that opportunity given?
Gold: The boosting data that we’ve shown is in the P-11 trial and that is in an earlier stage prostate cancer population. No patients in 9901, 9902a or IMPACT have been eligible for a booster. But we’re happy to talk about the concept of boosting if you’d like.
Monane: So no patients in this trial got a booster, correct:
Gold: Correct.
Monane: Did the company have any expectations of this analysis? Are you happy with this analysis? Disappointed? What have you really learned from this analysis in terms of Provenge development going forward and thinking about it as part of the company?
Gold: We’re encouraged by the data that we received by the IDMC. Consistency and reproducibility are one of the hallmarks of biological activity of any product, and the ability to impact survival, particularly in a disease like late stage prostate cancer, is potentially very meaningful. So the fact that we’re seeing data today—20% reduction in the risk of death—that’s very consistent with what we’ve seen in our previous Phase 3 trials and very encouraging to the company. As Greg and I have said when we meet with the investment community we always position the interim analysis as an opportunity to accelerate the regulatory pathway but that the final analysis, by design, has a higher probability of success. The fact that we shot a 20% reduction in risk today and that target we are shooting for in the middle of next year is a 22% reduction and that in our previous Phase 3 studies we’ve seen this increasing treatment effect over time, I think we’re looking forward to the results of the IMPACT study next year.
Miller: Do you assume that there would be a faster clean of the data next time or would it be back to the five months that it was this time?
Gold: I don’t think we can speculate on that. Mark’s team did a tremendous amount of work to get ready for this interim analysis and he had to do a tremendous amount of cleaning of the data to get it ready for the IDMC so I think it’s difficult to speculate on how long it will take…we’ll do it as rapidly as possible.
Miller: You wouldn’t have to repeat this on the patients that have died already?
Froelich: That’s correct.
Miller: Are you going to meet with the FDA on these data?
Froelich: This data has already been discussed with the FDA.
Miller: Anything you can characterize from their comments on it?
Gold: There really isn’t anything meaningful to discuss other than that we’re encouraged by the data and we didn’t meet the pre-specified criteria to be able to render an amendment to the BLA and we look forward to the final data.
We look forward to the final results of the IMPACT study in the middle of next year. In the meantime, we’ll continue to update you on our latest Phase 2 trials of Provenge and the other products in our pipeline that we’re excited about. Thanks for participating in the call and have a great day.
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Ocyan’s Analysis
Ocyan’s analysis:
http://tinyurl.com/43pwqb
http://tinyurl.com/3k6tqh
http://tinyurl.com/4jc8z
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Luke Timmerman on Trp-p8 (D-3263)
http://tinyurl.com/5ta2u7
http://tinyurl.com/5f64un
Neuvenge PR Nov 08
http://tinyurl.com/5pepjb
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Froggmisters Dendreon Research Blog
Provenge Science Overview provenge-science-overview.pdf
Scientific Publications http://www.dendreon.com/dndn/publications
Active Cellular Immunotherapy http://www.dendreon.com/dndn/pipaci
3/3/08 — Dendreon Publishes Manuscript on CD54 as a Surrogate Marker of Antigen Presenting Cell Activation
2/14/2008 — Dendreon Presents Data Correlating the Cumulative Potency of PROVENGE® to Overall Survival
1/2008 Nature Biotechnology 26, 1 (2008)Editorial: The regulator disapproves Abstract (click this link)
Pressure is mounting on the US Food and Drug Administration (FDA) to explain its decision to ignore an advisory committee’s positive recommendation for the cancer vaccine Provenge.
7/1/2007 Dr. Jeffrey Schlom — http://clincancerres.aacrjournals.org/cgi/content/abstract/13/13/3776
Cancer Vaccines: Moving Beyond Current Paradigms
Jeffrey Schlom, Philip M. Arlen and James L. Gulley
Authors’ Affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland
Requests for reprints: Jeffrey Schlom, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Room 8B09, 10 Center Drive, Bethesda, MD 20892. Phone: 301-496-4343; Fax: 301-496-2756; E-mail: js141c@nih.gov.
“In the randomized multicenter Sipuleucel study described above, patients in both the vaccine arm (n = 51) and placebo arm (n = 31) went on to receive docetaxel at progression. There was a striking and statistically significant (hazard ratio, 1.90; P = 0.023) increase in overall survival with docetaxel treatment in patients having had prior vaccine versus placebo (Fig. 4).”
A placebo-controlled randomized phase III trial in patients with metastatic asymptomatic androgen-independent prostate cancer using Sipuleucel-T has been reported recently (19). Patients were randomly assigned in a 2:1 ratio to receive vaccine (n = 82) or placebo (n = 45). The primary end point of this study, which was progression-free survival, did not achieve statistical significance (P = 0.052; Fig. 1A). Overall survival, however, was statistically significant (hazard ratio, 1.70; P = 0.01) between vaccine (25.9 months) versus placebo (21.4 months; Fig. 1B). A second randomized trial with Sipuleucel-T in this patient population showed a trend toward increased survival (19 months for vaccine versus 15.7 months for placebo) that did not reach statistical significance. Thirtysix- month survival was 32% for vaccine-treated patients versus 21% for placebo-treated patients. The integrated analysis of both of these randomized trials, vaccine (n = 147) versus placebo (n = 78), showed a statistically significant increase in overall survival (hazard ratio, 1.5; P = 0.011) in vaccine-treated patients. Thirty-six-month survival was 15% for placebo and 33% for vaccine.”
The abstract, titled “Advanced prostate cancer Patients who Receive Sipuleucel-T followed by Docetaxel Have Prolonged Survival” (#605), authored by Daniel P. Petrylak, M.D., associate professor of medicine at New York- Presbyterian Hospital at the Medical Center, is based on an exploratory analysis conducted to assess the influence of the active cellular immunotherapy PROVENGE on the clinical outcome of patients who subsequently went on to receive docetaxel chemotherapy after primary treatment with PROVENGE. The analysis was conducted by evaluating data from two Phase 3 clinical trials of PROVENGE in patient with asymptomatic, metastatic, androgen-independent prostate cancer (AIPC).
“The results of this analysis suggest that the use of sipuleucel-T as a first-line treatment followed by the chemotherapy docetaxel upon disease progression may provide patients with a substantially prolonged survival benefit,” said Dr. Petrylak. “This analysis provides valuable clinical insight as to how the treatment of men with advanced prostate cancer will likely evolve with the potential introduction of new products like sipuleucel- T that complement the currently available treatment regimens for men with advanced prostate cancer.”
7/1/05 — Journal of Clinical Oncology, Vol 24, No 19 (July 1), 2006: pp. 3089-3094
© 2006 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2005.04.5252
7/1/2005 — Placebo-Controlled Phase III Trial of Immunologic Therapy with Sipuleucel-T (APC8015) in Patients with Metastatic, Asymptomatic Hormone Refractory Prostate Cancer
Eric J. Small, Paul F. Schellhammer, Celestia S. Higano, Charles H. Redfern, John J. Nemunaitis, Frank H. Valone, Suleman S. Verjee, Lori A. Jones, Robert M. Hershberg http://jco.ascopubs.org/cgi/content/full/24/19/3089
David Miller of Biotech Research Rebuttal to Dr. Howard Scher’s “Leaked” Cancer Letter (click this link)
Walldiver & Company’s Rebuttal To Scher’s “Leaked” Cancer Letter (click this link)
Check back as we set up this page on the science behind provenge.
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