AUA 2013: No Cost-Effective Way to Save Lives from Prostate Cancer

May 6, 2013

SAN DIEGO — All of the current treatment strategies for castration-resistant prostate cancer (CRPC) exceed the generally accepted criteria for cost-effectiveness, according to an analysis reported here.

The least costly of the regimens exceeded the $100,000 threshold by about $60,000, and the most costly approached three times the threshold for willingness to pay per life-year saved.

The analysis did not incorporate the costs related to adverse events, palliative care, quality of life, or a number of other factors that could influence cost, Matthew Pollard, MD, of Mount Sinai Medical Center in New York City, said at the American Urological Association meeting.

“All current treatment options exceeded the societal threshold for willingness to pay of $100,000,” said Pollard. “However, the effectiveness of the current paradigm is likely to improve and costs are likely to reduce due to learning and competition that would potentially decrease the incremental cost-effectiveness ratio (ICER).”

After decades with few treatment options for men with metastatic CRPC, multiple agents have become available in the past few years. The emergence of new options and strategies gave rise to questions about the cost-effectiveness of different therapeutic approaches, said Pollard.

To estimate cost-effectiveness, investigators used data from randomized phase III clinical trials to establish a decision tree for use of available therapies in metastatic CRPC. Survival data and costs of interventions were incorporated into cost-effectiveness calculations.

On the basis of survival benefits associated with each therapy, Pollard and colleagues developed a model that incorporated a hierarchical therapeutic paradigm of sipuleucel-T (Provenge), followed by abiraterone (Zytiga), docetaxel, enzalutamide (Xtandi), and cabazitaxel (Jevtana). The analysis included a recently reported 78% response rate with sipuleucel-T, said Pollard.

Each treatment strategy evaluated included concurrent administration of leuprolide and denosumab (Xgeva). Cost-effectiveness was compared with the societal willingness-to-pay threshold of $100,000 per life-year saved.

The survival benefit associated with the therapies ranged from 2.4 months with cabazitaxel to 11 months with sipuleucel-T, resulting in a cumulative survival benefit of 23.4 months. Total cost of the individual therapies (including leuprolide and denosumab) was $361,954.

The investigators than calculated the costs associated with progression through the different strategies with the assumption that the reported survival benefit would be achieved with each drug used. Cost-effectiveness was defined by the ratio of the change in costs to incremental benefits (incremental cost-effectiveness ratio, ICER).

The calculations showed that sipuleucel-T + abiraterone + docetaxel was the most cost-effective approach, resulting in an ICER of $158,200, followed closely by sipuleucel-T alone ($159,532). Treatment that included sipuleucel-T, abiraterone, docetaxel, and enzalutamide resulted in an ICER of $221,812, and extending the strategy to include cabazitaxel produced an ICER of $271,460.

Omitting sipuleucel-T from the treatment paradigm resulted in an ICER of $157,143 for abiraterone + docetaxel, increasing to $193,788 for abiraterone alone. Adding enzalutamide and cabazitaxel to the strategy resulted in the same ICER values as in the calculations that included sipuleucel-T.

Pollock acknowledged several limitations of the analysis, including the inability to calculate quality-adjusted life-years, cost of palliative and other interventions, lack of information about true patterns of care for metastatic CRPC, and lack of survival data for sequential treatment.

“The treatment paradigm will continue to change,” said Pollard. “A better understanding of the quality-of-life outcomes will help to guide judicious use of available treatments.”

During the discussion that followed the presentation, David Penson, MD, of Vanderbilt University in Nashville, questioned whether the cost of the treatment strategies would decrease.

“The analyses included only the cost of the drug,” said Penson, who chairs the AUA health policy committee. “There are all of the indirect costs and also complications. Do you really think we will ever get below $100,000?”

Pollard acknowledged that a willingness-to-pay target of less than $100,000 might be out of reach. “I think we will get closer to $100,000, but I’m not sure we will ever be below $100,000.”

Session co-moderator Christopher Saigal, MD, of the University of California Los Angeles, viewed the exclusion of quality-of-life data as a strength of analysis by creating a “best case” scenario.

“If the drugs ever did get below $100,000, then you could look at adding quality of life and other factors,” said Saigal.