More on Sipuleucel-T (Provenge) from the 2013

The last two abstracts that I want to speak about that were presented at the conference that pertained to Provenge speak to its efficacy. The first looks at changes in circulating tumor cells (CTC) and the second to the onset of the use of opioid painkillers.

Abstract #40 evaluated the changes in circulating tumor cells (CTC) and markers of inflammation after sipuleucel-T treatment. In the study the researchers prospectively collected CTC, LDH, and inflammatory markers.

Men with castrate resistant prostate cancer (CRPC) had blood drawn routinely before and after treatment with Provenge. The researchers concluded: “We found that CTC counts can decline after (Provenge) treatment, including conversion from unfavorable to favorable range, and can change independently of PSA. Correlation of CTCs with outcomes in a prospective study is warranted to explore this as a potential biomarker.”

However, I do not agree with the investigators. Looking at the data which was:
1- The sample included 61 men who received Provenge at USC from June 2010 to July 2012.
2- The median pre-treatment PSA level was 24.9; 47% had Gleason 8-9 and 20% had received chemotherapy.
3- 15 of the 61 men had detectable CTCs pre treatment (range 1-170). CTC count declined in 7 men, increased in 6 men, and stayed stable in 2 men; in 3 cases the change crossed men over from unfavorable ( >5) to favorable count.
4- PSA declines were noted in 10 men (16.4%) ranging from -0.5% to 99%.
5- Change in CTC and PSA was discordant in 4 cases of 13. When CTC stayed stable PSA increased in 5 and decreased in 5 cases.

None of these changes are statistically significant, Despite the conclusions of the researchers I can not see how this research demonstrates the Provenge treatment positively or negatively effects CTCs or inflammatory response. CTCs, based on this research, are not a potential biomarker for the efficacy of Provenge.

Study by: Mehmet Hepgur – University of Southern California, Norris Comprehensive Cancer Center

The next abstract I want to review has more positive results for Provenge treatment. The abstract,#74 evaluated the relationship of Provenge with time to first use of opioid analgesics (TFOA) in men with metastatic castrate resistant prostate cancer (mCRPC). It used data collected from the IMPACT trial, the phase III trial that led to the FDA’s approval of Provenge.

Using a Cox regression model with adjustment for baseline PSA and LDH the researchers concluded that relative to placebo, Provenge delayed the TFOA in patients with asymptomatic or minimally symptomatic mCRPC, or men did not need to move on to opioid analgesics as quickly as did men who had a placebo..

Study by: Eric Jay Small – Helen Diller Family Comprehensive Cancer Center, University of California

In conclusion CTCs as well as PSA does not seem to be an adequate biomarker for a positive effect of Provenge. This does not mean that Provenge is not effective, it is, it does extend life. We will need to continue our search for other biomarkers. However, Provenge does delay the need for the use of our most powerful painkillers. These painkillers bring a host of additional detrimental quality of life issues, so this is clearly in the positive side for the use of Provenge.

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