Vogelzang Disputes 'Weak' Guideline Rating for Sipuleucel-T

Beth Fand Incollingo @fandincollingo
Published: Friday, Oct 03, 2014
Dr. Nicholas J. Vogelzang

Nicholas J. Vogelzang, MD

In a recent guideline for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC), the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) shared their thoughts on the implementation of six drugs approved since their previous recommendations were issued in 2007, as well as on older drugs.

In addition to recommending, with moderate strength, that androgen-deprivation therapy (ADT) be used indefinitely in these patients, the guideline also shares suggestions for the use of the six newer drugs concurrently with ADT.

Among the newer agents is the immunotherapy sipuleucel-T (Provenge). The guideline gives this drug a weak recommendation in the setting in which it was FDA-approved in 2010: for the treatment of asymptomatic and minimally symptomatic patients with mCRPC. As part of their rationale for the weak recommendation, the guideline authors explain that sipuleucel-T offers improved survival and low toxicity, but an unclear effect on quality of life. In addition, the guideline suggests that sipuleucel-T offers moderate benefit and low harm, with moderate evidence strength.

“Although controversies have been raised in editorials regarding the conduct of clinical research of this product, based on the trial results, it remains an option that may reasonably be discussed with patients who have a low symptom burden,” the guideline states.

An autologous cellular immunotherapy, sipuleucel-T targets prostatic acid phosphatase (PAP) as a means of boosting a patient’s immune system in the fight against cancer. The drug is tailor-made by using leukapheresis to collect immune cells (autologous antigen-presenting cells) from a patient’s own blood; the cells are then exposed to a protein (PAP linked to immune-cell activator granulocyte-macrophage colony-stimulating factor) and returned to the patient intravenously, according to the FDA, which notes that the product also contains T cells, B cells, natural killer cells, and other cells.1

The panel that wrote the ASCO/CCO guidelines considered data from the phase III IMPACT trial of sipuleucel-T,2 which demonstrated that men treated with the drug survived a median of 4.1 months longer than those in the control arm. Median overall survival was 25.8 months, versus 21.7 months, for a 22.5% reduction in risk (P = .032).

The guideline authors pointed out that there was no difference between the drug and placebo in the areas of prostate-specific antigen (PSA) level, objective disease progression, or grade 3 to 5 adverse events, and that quality of life information was not reported in the trial.

To gain insights about the use of sipuleucel-T in this population of men, and to seek an expert opinion about the position taken on the drug in the guideline, Urologists in Cancer Care spoke with Nicholas J. Vogelzang, MD, site research leader at the Comprehensive Cancer Centers of Nevada and a member of the US Oncology Network. A collaborator on the IMPACT trial, Vogelzang uses sipuleucel-T regularly in patients and gives lectures about the treatment on behalf of its developer, Dendreon.

UCC: How frequently, and in which types of cases, do you give sipuleucel-T—and why?

Vogelzang: I’ve treated about 150 men with Provenge so far, and I recommend it to every one of my prostate cancer patients who have metastatic disease.

We don’t fully understand how Provenge works, so I can’t say that it’s working well. But we know it works better when PSA is low, and we’ve done a lot of studies to show a profound upregulation of the immune system by the drug.

I have anecdotal cases, such as a patient, a veterinarian from Utah, whose PSA became very low with a combination of [the immunotherapeutic vaccine] Prostvac followed by Provenge. But I’m not counting on that happening regularly. I have other patients whose PSAs keep rising rapidly. That’s frustrating to the doctor and the patient, but it doesn’t mean I’m not going to try Provenge on everyone appropriate for the therapy.

I believe Provenge is an important component of managing prostate cancer. It certainly beats chemotherapy, Zytiga [abiraterone], or Xtandi [enzalutamide] in terms of side effects. That’s why I do not understand the guideline’s comments about quality of life. Anyone who has used the therapy understands that it’s ideal for older patients. It prolongs survival at a very low physical cost, and is fully reimbursed with few out-of-pocket costs to the patient.

What is your opinion of the ASCO/CCO guideline’s “weak” recommendation that physicians administer sipuleucel-T to men with mCRPC who are asymptomatic or minimally symptomatic?

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