Is “pricey” Provenge a harbinger of biotech woes?

According to the survival data, Provenge survival advantage comes with no evidence that the therapy shrinks tumors or even delays tumor growth. Although this somewhat counter-intuitive outcome of the Provenge clinical trials did not dissuade FDA approval, some experts are questioning whether we can afford to pay for wildly expensive drugs in a time of economic crisis.

A New England Journal of Medicine editorial by Dan L. Longo, MD, called the ability of Provenge to prolong the survival in prostate cancer patients without having any measurable effect on the tumor is called “surprising” and “hard to understand.”

Dr. Longo, however, raised the issue again in his NEJM editorial:

“The prolongation of survival without a measurable antitumor effect is surprising,” Dr. Longo wrote. “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. This lack of tumor effect raises concerns that the results could have been influenced by an unmeasured prognostic variable that was accidentally imbalanced in study-group assignments.”

Provenge is priced at $93,000 per course of treatment, which Dr. Longo labeled as a “concern.”

"The high cost may affect use. It is also uncertain what role sipuleucel-T [Provenge] will ultimately play in the treatment of prostate cancer, given the other promising treatments in development,” he wrote. Longo goes on to mention other prostate cancer drugs in late-stage clinical trials, including Johnson & Johnson’s abiraterone and Medivation’s MDV3100.

“The prospects for improved therapy for prostate cancer have never been so encouraging,” Dr.  Longo concluded at the end of his editorial. “The poor prognosis for men with prostate cancer will probably be substantially improved by the findings that emerge from ongoing clinical research.”

Results of the published IMPACT study also showed that:
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• The survival benefit associated with PROVENGE was observed consistently across multiple patient subgroups, including those with prognostic factors known to be adversely correlated with overall survival, such as PSA, LDH, alkaline phosphatase, number of bone metastasis, Gleason score, performance status, and presence of pain;
• Of patients that received PROVENGE, 97.1% received at least one infusion and 92.2% received all three infusions.  In addition, the median time from the first to the third infusion was 28 days;
• Sensitivity analyses provided no evidence that the use of docetaxel could account for the observed treatment difference with respect to overall survival;
• Results were consistent with and confirmed the findings of D9901, a phase III, randomized trial, in which the PROVENGE group had a median increase in survival of 4.5 months, a median survival of 25.9 months, and a 3-year survival rate of 34.1%;
• The time to objective disease progression was similar in the two study groups and consistent with results from other trials in this patient population; and
• Overall, 0.9% of patients in the PROVENGE group were unable to receive all three infusions because of infusion-related adverse events.