Picture an active, mentally acute man with prostate cancer who loves life, loves his family, and is described by his urologist as being “remarkable” and possessing “incredible resilience.”

Twenty-two years after a radical prostatectomy the man now has extensive disease, including liver metastasis, but he continues to enjoy a good quality of life. The man is a strong and eager candidate for a brand-new treatment that could extend his life by several months with relatively few side effects that will allow him to maintain a pleasant existence. But there’s a catch: The treatment costs about $93,000 and the patient is 93 years old.

The man really exists. Since 1988, he has been a patient of Thomas M. Pitre, MD, of Northwest Urological Clinic, PC, in Portland, Oregon, and Oregon Health Science University. Implications for the U.S. health system at large aside, Dr. Pitre is pleased that the oncologist on the case is indeed making the request to obtain the treatment, called Provenge (sipuleucel-T). Made by Dendreon, Provenge is the first FDA-approved autologous cellular immunotherapy.

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While acknowledging that “we don’t have enough resources to provide everything to everybody, when we’re talking about an individual human life, we’re talking about the relationship of a physician with his patient,” Dr. Pitre said.

This helps illustrate bioethical issues surrounding Provenge. In the harshest and least sentimental terms, an astronomically expensive intervention that prolongs life for a modest period for mostly elderly patients may not represent the most cost-effective use of health-care resources. Men with advanced prostate cancer, however, are not some ill-defined subpopulation to their loved ones or to their urology specialists. They are individuals.

“It’s a little difficult to have individual American clinicians having to try to make societal discussions and decisions when they’re sort of confronted with their own patients,” affirmed Robert Dreicer, MD, a urologic medical oncologist and Chairman of the Department of Solid Tumor Oncology at Cleveland Clinic’s Taussig Cancer Institute.

“Look, we all understand that as therapeutics for cancer and other diseases evolve, novel therapies will come online, and all of these therapies are very expensive and we don’t have unlimited resources. And of course we discuss this at meetings and such, but when the rubber hits the road and you’re sitting with an individual patient, you’re not going to say, ‘Today, I’m going to have society’s best interest in mind but not my patient’s.’ It’s very difficult.”

“I can’t imagine that there are going to be a lot of urologists who are going to say, ‘Don’t take this drug; it isn’t worth it,’ given the age of the people, given the relatively modest side-effect profile, and given the demonstrated modest improvement of survival,” said Baruch A. Brody, PhD, a professor of medicine and biomedical ethics and Director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine in Houston.

“You know, if you tell me I can have a few more months of relatively symptom-free survival, and you’re willing to pay for it for me, it’s not immediately evident to me what the downside would be, and I suspect there’s not going to be many other people who think there is a downside. That’s why [making Provenge available] is going to be such a hard case for society to figure out.”

Dr. Brody, who has served on many bioethics advisory and data safety monitoring boards for a range of studies, is familiar with the challenges of Provenge—past as well as present. He wrote about the therapy after the FDA decided to defer approval of the drug application in 2007.

This move as well as subsequent negotiations between the FDA and Dendreon regarding what an acceptable clinical trial for the vaccine would be resulted in the 512-patient Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) study that ultimately brought Provenge to market. Dr. Brody was again on the scene when debate raged anew in 2009, with leading biostatisticians questioning why Dendreon had been given access to—and then publicized—data from an interim analysis of IMPACT.

Provenge was finally approved on April 29, 2010, for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210215.htm), The treatment is administered in three doses—one intravenous infusion approximately every two weeks—at a cost of about $31,000 per infusion, or $93,000 for the full regimen, and yields a 4.1-month median improvement in survival (25.8 months for treated patients vs. 21.7 months in controls in IMPACT). “Putting it very crudely, you’re paying about $23,000 for each month of additional survival,” Dr. Brody observed.

Because the 4.1 months is a median, that means survival could be less and could be more. “It still comes down to $23,000 a month, and that’s one of the big issues that’s obviously being raised,” Dr. Brody stated. “In an article I read, somebody posed the question, ‘Will patients be able to pay that?’ And of course that’s silly, because patients don’t pay for that. These are overwhelmingly people who are on Medicare, and the question is going to be, is Medicare willing to pay $23,000 per extra month of life?”

As Dr. Brody noted, balancing the cost to some degree is Provenge’s favorable risk profile: The most common complaints are chills, fatigue, fever, back pain, nausea, joint ache, and headache, although more serious respiratory or cardiovascular disorders are possible. “And remember, the average age of the patients tested was [only] 71, and they are basically asymptomatic so they’re not in terrible pain,” he pointed out. “So from the perspective of the patient, getting four more [relatively comfortable] months looks like a good deal. And from the perspective of physicians, how can they not at least suggest—if not strongly recommend—that the patient take this drug? The only crucial question is from the perspective of the society.”

Cleveland Clinic’s Dr. Dreicer is familiar with the issues raised by Provenge, and believe they characterize the questions inherent in the U.S. health-care system in general. As he described it, “Individual patients [with advanced hormone refractory prostate cancer] look at Provenge and say, ‘This is the most significant change in survival for an intervention for advanced prostate cancer that is currently available, and it’s a relatively nontoxic therapy.’ But then from the health-economic or societal perspective, you ask the question, ‘But is it really worth it?’”

The answer, according to Dr. Dreicer, depends on one’s perspective. “In a setting with unlimited resources, it’s a relatively easy question. In a setting in which there are limited resources but we don’t act like there are limited resources, it’s a very complicated scenario.”

Nevertheless, Dr. Dreicer acknowledged, the reality is that physicians in America work within a system that historically has allowed them to try to provide the best therapy for patients. “In this system, cost has always been an issue, but it has not reached a level of interference with practice that it does in lots of parts of the world, where decisions about bringing certain therapies online don’t only take into consideration whether the therapy is useful, but whether it’s cost-effective.” (See sidebar for opinions on whether the FDA should take the same tactic.—Eds.)

Urologist Dr. Pitre, who has a special focus in bioethics, looks at Provenge this way: “I think the issue is not just how much is too much in the area of cost but also when do we stop advancing our ability to treat serious disease.  What we’re dealing with here is the perfect poster child for a major advance that’s costly [but prompts the question of ] where and how do we draw the line in the costly development of new therapies – should a free market decide or should there be regulation that may stifle research.”

“In my view, the only bioethical issue that Provenge represents is the issue of cost, in terms of that entering into the equation of [financial] burden, and then who bears the burden, and what model,” Dr. Pitre said. “And that has a lot to do with a lot of the various ways that people are looking at new paradigms of health-care reimbursement.”