More on Provenge –How beautiful the Emperor’s Clothes?

Provenge is innovative, very expensive and minimally effective. It won’t cure disease but will provide a very slight 9% improvement in those alive at 3 years–that’s less than a 1 in 10 benefit.

The cost is $93,000 for a full treatment. It’s not clear whether repeat courses can be given.

To put in perspective consider that a more conventional chemotherapeutic agent docetaxol (Taxotere) provides a 3 month benefit at significantly less cost.

Here is a detailed review of this drug’s efficacy:

The two trials used 2:1 randomization, with patients to receive Provenge or placebo three times, with 2 weeks between each treatment. Study 1 randomized 82 men (median age 73; 89% white) to Provenge and 45 (median age 71; 93.3% white) to placebo. The treatment group had a nonsignificant median time to progression of 11.0 weeks, compared with 9.1 weeks in the placebo arm (P = .085). (Medicynical emphasis)

After study 1 failed to meet its primary endpoint, researchers halted enrollment in study 2 following accrual of 98 of 120 planned patients with similar age and racial characteristics as those in study 1. (The difference in time to progression in the second study also was nonsignificant, 10.9 weeks for Provenge vs 9.9 weeks for placebo (P = .719). The two trials found no significant regression in tumor size among the treated patients. (Medicynical emphasis)

Although neither study specified overall survival as an endpoint, a post hoc analysis of the study 1 data showed an overall median survival benefit for the Provenge arm, compared with placebo, of 25.9 months vs 21.4 months (P = .01). “

An analysis of study 2 found a median overall survival of 19 months for the treatment arm vs 15.7 months for the placebo group, a difference that failed to reach statistical significance (P = .331). “It should be noted that the survival time in this study was shorter than the counterpart in study 1, which suggests that significant populations in these two studies may not be exactly the same,” remarked FDA clinical reviewer Ke Liu, MD, PhD. Dendreon also presented combined overall survival data from the two trials, showing a significant advantage for Provenge, 23.2 weeks vs 18.9 weeks for placebo (P = .011)

link: Substantial Evidence for Provenge Efficacy: FDA Panel – Cancer Network

And this from a later study:

In clinical trials, Provenge extended survival by a median 4.1 months — about half of patients were below that amount and half were above. But some of the patients remain alive years after the treatment. In the most recent trial, 32% of Provenge-treated patients remained alive three years after treatment. Only 23% of placebo-treated patients survived that long. (Medicynical Emphasis– It’s not stated whether patients receiving placebo also remain alive years after the treatment)

link: FDA OKs Provenge for Prostate Cancer Therapy

Of interest is that more patients in the study group received docetaxol (Taxotere) 57% vs 50.3% in the placebo group after signs of disease progression. As in many drug comparison trials the matching up of the groups is essential to the validity of the study. It’s conceivable given the small size of the study that normal biologic variation in the diseases course and the differences in patient management could account for much of the “evidence” of efficacy.

There is a long history of study results often sponsored by drug companies that were viewed as “significant” that later turned out to be simply artifact–see Premarin and erythropoietin data to name two examples.

Medicynical Note: After three years survival in the treated group was 9% better than those receiving absolutely nothing–a placebo.

Provenge does not appear to work with the more malignant Gleason 8-9 varieties of the disease.

However, according to information supplied by Dendreon, analysis of the data for pre-specified variables revealed Gleason score as the single most important predictor of response to Provenge®. In patients with a Gleason score = 7 who received Provenge®, the likelihood of remaining progression free and free of cancer-related pain while on study was over twice that of men who did not receive Provenge®. In addition, those patients receiving Provenge® whose disease had not progressed six months after randomization, had a greater than eight-fold advantage in progression-free survival compared to those patients who received placebo (35.9% versus 4%). In contrast, the benefits of Provenge® therapy were not seen in patients with a Gleason score = 8.

link: Prostate Cancer Research Institute – Update on Provenge Trials

This is an advance but it also is a very limited benefit from a very expensive drug. Would you buy a car for $100,000 that lasted months? Would you go into debt to get this drug? Would you sell your house to raise funds to have access?

Drug companies became alchemists in the mid 90’s when they discovered that patients with fatal illness were neither cost aware nor cost sensitive. Any minor advance that offer a modicum of success even as little as a 10% chance of living a month or two or four longer was worth spending huge sums of money. They don’t justify the pricing by their costs or the efficacy of the drug, they simply point out that other drug companies charge similarly for similarly ineffective agents.

Drugs like Provenge, that have interesting mechanisms of action with minimal efficacy are money cows for the pharmaceutical industry. The question is how much longer can they ride this gravy train, before the emperor is shown to have no clothes? And/or the system crashes?

More here.

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