Real-world survival benefit of treatment with sipuleucel-T

So there are new, interesting data regarding the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) with sipuleucel-T (Provenge) as well as either or both of abiraterone acetate (Zytiga) and enzalutamide (Xtandi) — known generically as androgen-receptor signaling pathway inhibitors or ASPIs. However, these data need to be assessed with some caution at this time.

The new data come from an article by McKay et al. in Advances in Therapy. The authors report retrospective, observational data from > 6,000 men with advanced prostate cancer in the US who were chemotherapy naive and who had continuous Medicare eligibility (Parts A, B, and D, but not Part C) over a 3-year observation period between 2014 and 2017. The entire text of this article is available on line, and so anyone can read the original article for themselves.

According to McKay et al., their patients all had to have been mCRPC-treatment-naïve men who had had no previous FDA-approved treatment for mCRPC for 12 months before any initial claim (in 2014) for treatment of mCRPC, with the exception of standard forms of androgen deprivation therapy (ADT). The patients were then all required either to have continuous coverage for 36 months or to have died.

Here is a basic summary of their findings:

  • The data set included 6,044 eligible men with mCRPC of similar levels of disease severity.
  • The average (median) overall survival (OS) for the entire set of 6,044 patients was 23.0 months
  • When sipuleucel-T was administered to patients at any time during the 3-year observation period, the median OS was
    • 35.2 months for the 906 patients who received sipuleucel-T and at least one ASPI
    • 20.7 months for the 5,092 patients who received no sipuleucel-T
    • The adjusted hazard ratio (aHR) was 0.59
  • When sipuleucel-T  was administered to patients as first-line therapy during the 3-year observation period, the median OS was
    • 34.9 months for the 647 patients who received sipuleucel-T and at least one ASPI
    • 21.0 months for the 4,810 patients who received no sipuleucel-T
    • The aHR was 0.56

McKay et al conclude that their analysis suggests:

… use of sipuleucel-T at any time was associated with improved OS compared with ASPI use alone.

However, they are also careful to point out that their analyses

… are intended as descriptive rather than definitive as this dataset contains limited data on key clinical factors.

and that

While selection bias is a risk in secondary claims data, this research provides important insight into real-world treatment outcomes.

The only way to clearly demonstrate whether combined, sequential treatment of men with newly diagnosed mCRPC with sipuleucel-T and an ASPI as opposed to just ASPIs would be through an appropriately constructed, randomized clinical trial. However, whether any company or other funding body would be willing to cover the costs of such a trial (which might require something like1500 patients) is open to question.

The real issue is going to be whether, given the apparent size of the extension of survival times (of about 14 or 15 months) for these patients with mCRPC if they are treated with both sipuleucel-T and an ASPI, someone can justify the cost of such a trial. Should the results of such a trial be positive, however, it might siognificantly alter the standard of care for men with metastatic disease who become castration-resistant after initial treatment with standard forms of ADT.

2 Responses

  1. I was diagnosed with advanced, metastatic prostate cancer, stage D2 (Stage IV) 11/17. PSA of 1,323 ng/ml. Bicalutamide/Lupron Depot lasted a year to PSA @ 1.75 ng/ml before cancer beat it. Next was Xtandi/Eligard, 1 year until insurance agreed to swap as PSA steadily but slowly rising every month to 313.15 ng/ml. Zytiga/Eligard next. Failed in 2 months, during which PSA climbed to 1,203.58 ng/ml. mCRPC obviously now. Docetaxel/Eligard next. Took three infusions to get traction (by which time PSA was 1359.48 ng/ml) and start depressing it. Now 877.32 ng/ml after fifth infusion; sixth pending. No faith in Xtandi or Zytiga here. If sipulecel-T is dependent on them for androgen blocking, I doubt the benefit, at least for me.

  2. The key to success with sipileucel-T, in the words of its PI, Larry Fong, is “a long landing strip”, otherwise interpreted as low PSA at the time of receiving Provenge.

    The treatment has always gotten a bad rap for having such short benefit for an expensive treatment, but this may not be so true if correlated with PSA. This is briefly referred to in the discussion section of the referenced article, where lower PSA levels in post-hoc results for the original IMPACT study that gained the FDA approval showed 50% better 3-year relative survival for men in the lowest quartile of PSA (< 22.1 ng/ml).

    This study also refers to comparable studies showing good results for Provenge at PSA levels 300 ng/ml, experience sadly doubts that sipuleucel-T will be effective.

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