Quest Summer 2012 : Page 9

P r o v e n g e The Latest Controversy by Cecilia Lacks, PhD P hysicians want new treatments to work, especially for patients who no longer respond to existing treatments. Provenge, Sipuleucel-T, was one of those hoped for new treatments. After being rejected by the FDA in 2007 and 2009, it was approved by the US Food and Drug Administration in 2010 as an immunotherapy for late-stage prostate cancer. It was controversial from the get go because it didn’t appear to affect disease progression and no evidence was presented to show it killed tumors. It was exorbitantly expensive, about $93,000 for a series of three infusions. Additional evidence showed that it appeared Dr. Catalona at the 90th annual to prolong life for a few meeting of the months in those over 65 Clinical Society but not those under, the of Genitourinary opposite of what one Surgeons. He was President of might expect. Even that evidence the Clinical Society for the of a few months 2011 year. extended survival is only by comparison to a placebo group of men age 65 and over. And then, the results on the placebo group over 65 did not take into account the effect of removing 20 billion mononuclear white blood cells and not replacing them. Still, for men with late-stage prostate cancer, it seemed to provide hope that a new therapy, immunotherapy, could prolong life by a few months and, with more research, provide real help. Dr. Catalona was concerned enough about Provenge that he wrote an article with his reactions in the Fall 2010 Q UEST , My Concerns About Provenge Vaccine , (See www.drcatalona.com in archives of past Q UEST s.) In it, he said: I am concerned that information to the public has presented an unjustifiably optimistic view of vaccine therapy for prostate cancer and unrealistically suggests that Provenge will usher in a new era of cancer treatment more effective than Q UEST Summer/Fall 2012 surgery, radiation, or hormonal therapy. In addition, from the data I have seen, I am skeptical that it will add materially to the treatment of patients with advanced-stage prostate cancer. Now, an article published in the Journal of the National Cancer Institute (JNCI) by lead author Marie L. Huber, has At first look, some things appear so perfect, but a reignited the controversy. closer observation reveals flaws, such as those on the The JNCI article begins by stating: The absence of supportive leaves, that change the reality of the subject. data has raised the concern that and 35% are returned. Patients lose 20 the 4.1-month survival benefit [from billion cells whose normal role is to Provenge] could be the result of a flaw in suppress their cancer,” Huber said. the trial design or from the chance All physicians want treatments to imbalance of unmeasured prognostic work. And Dr. Catalona, with his variables. research collaborators, is working hard We have reconsidered these trial results on research to improve treatments for in light of unpublished data obtained from prostate cancer and to discover the internal FDA documents that became reasons for and the prevention of available only after the approval of aggressive prostate cancer. sipuleucel-T. “We want and need to provide both We believe that analysis of the data in care and hope, but false hope with their totality challenges the published possible detrimental care will do no one interpretation of the trial results and any good,” suggests a different Dr. Catalona said. conclusion about the As the JNCI efficacy, and potentially article states: The safety, of sipuleucel-T. safety of prostate Because these data cancer patients as well have not been debated as the judicious publicly, we hope that development of this commentary will All over the world, people want an easy beneficial stimulate consideration cure for medical and health problems, immunotherapies of their implications. but it doesn’t work that way. depends on addressing According to the concerns raised and considering all Huber, “The most logical explanation of possible interpretations of the…trial the data I’ve seen is that Provenge results. treatment is harmful for older men and, at best, does nothing for men under 65. *Link to site prepared by Marie Huber: If my dad were a patient, I’d talk him http://theprovengetrials.org through the facts before he made any **(Link to complete JNCI article, Interdisciplinary treatment decisions. Critique of Sipuleucel-T as Immunotherapy in “First and foremost, I’d want my dad Castration-Resistant Prostate Cancer ) http://jnci.oxfordjournals.org/content/104/4/273.f to understand that to make Provenge, ull?sid=bbd4986a-61f1-4efe-9128-8a8cfd435ff2 over 90% of a man’s circulating (JNCI is not affiliated with the US National Cancer mononuclear white blood cells are Institute but it is a peer reviewed, prestigious harvested; 65% are lost in manufacture; scientific journal.) 9 ©photo by David Coblitz

Provenge

Cecilia Lacks, PhD

The Latest Controversy<br /> <br /> Physicians want new treatments to work, especially for patients who no longer respond to existing treatments. Provenge, Sipuleucel-T, was one of those hoped for new treatments. After being rejected by the FDA in 2007 and 2009, it was approved by the US Food and Drug Administration in 2010 as an immunotherapy for late-stage prostate cancer.<br /> <br /> It was controversial from the get go because it didn’t appear to affect disease progression and no evidence was presented to show it killed tumors. It was exorbitantly expensive, about $93,000 for a series of three infusions.<br /> <br /> Additional evidence showed that it appeared to prolong life for a few months in those over 65 but not those under, the opposite of what one might expect.<br /> <br /> Even that evidence of a few months extended survival is only by comparison to a placebo group of men age 65 and over. And then, the results on the placebo group over 65 did not take into account the effect of removing 20 billion mononuclear white blood cells and not replacing them.<br /> <br /> Still, for men with late-stage prostate cancer, it seemed to provide hope that a new therapy, immunotherapy, could prolong life by a few months and, with more research, provide real help.<br /> <br /> Dr. Catalona was concerned enough about Provenge that he wrote an article with his reactions in the Fall 2010 QUEST, My Concerns About Provenge Vaccine, (See www.drcatalona.com in archives of pastQUESTs.)<br /> <br /> In it, he said: I am concerned that information to the public has presented an unjustifiably optimistic view of vaccine therapy for prostate cancer and unrealistically suggests that Provenge will usher in a new era of cancer treatment more effective than surgery, radiation, or hormonal therapy.<br /> <br /> In addition, from the data I have seen, I am skeptical that it will add materially to the treatment of patients with advanced-stage prostate cancer.<br /> <br /> Now, an article published in the Journal of the National Cancer Institute (JNCI) by lead author Marie L. Huber, has reignited the controversy.<br /> <br /> The JNCI article begins by stating: The absence of supportive data has raised the concern that the 4.1-month survival benefit [from Provenge] could be the result of a flaw in the trial design or from the chance imbalance of unmeasured prognostic variables.<br /> <br /> 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.<br /> <br /> 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.<br /> <br /> Because these data have not been debated publicly, we hope that this commentary will stimulate consideration of their implications.<br /> <br /> According to Huber, “The most logical explanation of the data I’ve seen is that Provenge treatment is harmful for older men and, at best, does nothing for men under 65. If my dad were a patient, I’d talk him through the facts before he made any treatment decisions.<br /> <br /> “First and foremost, I’d want my dad to understand that to make Provenge, over 90% of a man’s circulating mononuclear white blood cells are harvested; 65% are lost in manufacture; and 35% are returned. Patients lose 20 billion cells whose normal role is to suppress their cancer,” Huber said.<br /> <br /> All physicians want treatments to work. And Dr. Catalona, with his research collaborators, is working hard on research to improve treatments for prostate cancer and to discover the reasons for and the prevention of aggressive prostate cancer.<br /> <br /> “We want and need to provide both care and hope, but false hope with possible detrimental care will do no one any good,” Dr. Catalona said.<br /> <br /> As the JNCI article states: The safety of prostate cancer patients as well as the judicious development of beneficial immunotherapies depends on addressing the concerns raised and considering all possible interpretations of the…trial results.<br /> <br /> * Link to site prepared by Marie Huber: http://theprovengetrials.org <br /> <br /> *(Link to complete JNCI article, Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in Castration-Resistant Prostate Cancer) <br /> <br /> http://jnci.oxfordjournals.org/content/104/4/273.f ull?sid=bbd4986a-61f1-4efe-9128-8a8cfd435ff2 (JNCI is not affiliated with the US National Cancer Institute but it is a peer reviewed, prestigious scientific journal.)

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