ASCO/CCO Recommendation on Sipuleucel-T Makes No Sense to 2 Clinicians Who've Used the Therapy

Evidence-Based Oncology, November 2014, Volume 20, Issue SP16

In September, the American Society for Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) released the first guideline on metastatic castration-resistant prostate cancer (mCRPC) since 2007, incorporating information on 6 new therapies that have changed treatment significantly in recent years.

Among the more controversial recommendations is the “weak” guideline rating for sipuleucel-T in the setting for which it was approved by FDA in 2010: treatment of asymptomatic and minimally symptomatic patients with mCRPC. Authors of the guideline stated that this first-in-class immunotherapy, marketed as Provenge by Dendreon, offers improved survival and low toxicity, but that its effect on quality of life is unclear. In addition, the guideline suggests that sipuleucel-T offers moderate benefit and low harm, with moderate evidence strength.1

Sipuleucel-T is an autologous cellular immunotherapy that targets the enzyme prostatic acid phosphatase (PAP) as a way to boost the patient’s own immune system to find the cancer. The therapy is manufactured using a patient’s own cells through a process called leukapheresis, to isolate the patient’s white blood cells; the cells are then combined with a protein that acts as an immune activating agent, and administered to the patient intravenously.2

Two clinicians who have treated patients with sipuleucel-T, one of whom is the second author on the study that preceded FDA approval, said in separate interviews that they cannot understand the rationale for the “weak” recommendation, given the evidence. However, so far, neither Nicholas J. Vogelzang, MD, site research leader at the Comprehensive Cancer Centers of Nevada, nor

Celestia S. Higano, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, has heard of any patient being denied coverage for sipuleucel-T on the basis of the ASCO update.

Higano noted that the ASCO guideline differs from the guidelines published by the National Comprehensive Cancer Network (NCCN); she suggested that if a patient has a challenge with coverage, he or the physician should point to the NCCN guideline.

In March, Higano discussed the benefits of sipuleucel-T at the 19th Annual NCCN Conference: Advancing the Standard of Cancer Care, where guideline updates were presented and discussed. In Higano’s presentation last March and in an interview recently conducted with Vogelzang, both keyed on what appears to be a stumbling block for those who have not embraced sipuleucel-T: because it has a mechanism of action different from chemotherapy, prostate-specific antigen (PSA) may not drop. Vogelzang said, “There’s a pervasive PSA-driven bias.…Doctors just don’t believe a drug works unless PSA drops.”2,3

Higano, in her interview, kept returning to the 2010 study in the New England Journal of Medicine, which she coauthored. She sounded frustrated with the ASCO panel’s conclusions in face of “Level 1 evidence and a 4-month survival benefit over placebo.” In the study, patients with sipuleucel-T had a median survival benefit of 4.1 months at 3 years, with a 22% reduction in the risk of death over a 3-year period.4

“How do you end up with this recommendation? It just doesn’t add up to me,” she said, later adding that it’s “not rational” for some physicians to “pick and choose” which data to believe.

“How can you completely dismiss a phase 3 clinical trial that has been peer reviewed in The New England Journal of Medicine?”

Some of sipuleucel-T’s harshest critics are from the United Kingdom, where the National Institute for Health and Excellence (NICE) last month refused to recommend the therapy for prostate cancer patients, purely for cost reasons. However, British outlets covering the NICE decision noted that getting the immunotherapy to patients overseas would present a different set of manufacturing and shipment challenges than those found in the United States.5

Both Higano and Vogelzang soundly rejected arguments that the ASCO recommendation might have been influenced by the drug’s cost. First, Vogelzang said, the fact that the therapy is administered differently from others does not mean it is more expensive, especially when the lack of side effects is taken into account. And second, both Higano and Vogelzang said that, as physicians, it’s their job to make the best therapeutic options available to their patients.

Sipuleucel-T is administered in 3 doses costing $31,000 each over a 5-week period. A standard chemotherapy option, enzalutamide, costs $8000 a month, Vogelzang said; if a patient takes it for 12 months, the costs are roughly the same, and some patients take it longer. “I cannot understand why there is a focus on monthly cost versus total cost,” he said.2

He added, “If you wanted to make cost the primary issue in treating patients, you could argue that we’d save a lot of money rapidly if we simply required surgical castration.”2

Despite the ASCO committee’s decision, Higano said that, from her vantage point, immunotherapy in cancer treatment generally is taking off, and that this incident is not going to stop progress in the use of immunotherapy to treat prostate cancer. “It’s going to go forward anyway,” she said.References

1. Incollingo BF. New ASCO/CCO mCRPC treatment guideline incorporates latest approved drugs. OncLive. Published September 8, 2014. Accessed October 24, 2014.

2. Incollingo BF. Vogelzang disputes “weak” guideline rating for sipuleucel-T. OncLive. Published October 3, 2014. Accessed October 24, 2014.

3. Caffrey MK. Understanding which therapy comes first in treating castration-resistant prostate cancer. Am J Manag Care. 2014;20(SP7):SP208-SP209.

4. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422.

5. Cost to NHS of providing sipuleucel-T too high to be recommended in draft guidance [press release]. London, UK: 2014; National Institute for Health and Care Excellence. October 16, 2014.