Despite its approval five years ago sipuleucel-T (Provenge) remains one of the most controversial treatments available for men with castrate resistant metastatic prostate cancer (mCRPC). Provenge has its advocates (Full Disclosure- I am) and it has many detractors. The detractors argue that it doesn’t work and they hang their hat on the argument that it doesn’t affect the PSA nor disease progression, which is true. Additionally, there was an earlier, now debunked, argument that there was fraud involved in the phase 3 IMPACT trial that derived the data that led to Provenge’s being approved by the FDA.

Since Provenge’s approval the treatment of mCRPC has changed with the addition of many more treatment options as well as the development of a more sophisticated understanding of immunotherapy.

Dr. Leonard G. Gomella, professor and chairman of the Department of Urology at the Sidney Kimmel Cancer Center, Thomas Jefferson University, discussed positively the use of Provenge at the 8th Annual Interdisciplinary Prostate Cancer Congress.

Dr. Gomella re-examined the IMPACT trial, which was the basis of the FDA’s decision to approve Provenge (sipuleucel-T) in 2010. He also discussed the benefits, limitations, and considerations of sipuleucel-T for men with prostate cancer.

According to Dr. Gomella data shows that Provenge needs to be used at the earliest stages of prostate cancer, before men become symptomatic, but after they become castrate resistant. He said that Provenge cannot be used if a man has liver metastasis, and you can’t use it with visceral metastasis; it really has to be used for bone-only mCRPC.

Dr. Gomella also pointed out there was some very interesting retrospective work done by Dr. Paul F. Schellhammer and associates examining the original IMPACT trial, which led to the approval of Provenge. Dr. Schellhammer found that if you looked at PSA and you broke it down in PSA ranges of less than 22, 22-50, 50-134, and above 134, there was almost a stair-step progression in the survival increases, with the earlier PSA levels being the lowest. In fact, the most pronounced survival averages, sometimes going over 42 to 44 months, were of patients who received Provenge with a PSA of less than 22.

Dr. Gomella also mentioned that he currently has a paper under review for where he states that Provenge works better than the IMPACT trial even suggested. His premise is that in the men in the placebo arm who progressed were given a secondary treatment with Provenge (or they were allowed to crossover to the treatment arm, but still be counted in the placebo arm for statistical purposes). He pointed out that there was a lot of men in the placebo arm were ultimately were treated with a modified form of Provenge based on frozen cells. This crossover would clearly dampen down the survival benefit difference between the placebo arm and the treatment arm.

I remain convinced that Provenge, when administered early on in prostate cancer disease progression is a viable and valuable tool which must be used to fight advanced prostate cancer. There is no question that it is very expensive, but when you weigh it against the real costs of other cancer treatments its cost are muted.

http://www.onclive.com/conference-coverage/ipcc-2015/Gomella-Discusses-Optimizing-Sipuleucel-T-in-mCRPC

Joel T. Nowak, M.A., M.S.W.