Code Description HCPCS
Q2043 Sipuleucel-T, minimum of 50 million autologous CD54+ cells activated with PAP-GMCSF, including leukapheresis and all other preparatory procedures, per infusion (Provenge®)
Cellular Immunotherapy for Prostate Cancer
Immunotherapy is a way to fight disease, even cancer, by using a person’s own immune system. Dendritic cells are part of the immune system. They help the immune system spot cancer cells. When the dendritic cells find and start to break down cancer cells, other immune cells are activated to also attack the cancer cells. In some cases of advanced prostate cancer, a vaccine can be made using a person’s own immune cells. Certain immune cells are removed, treated in a lab to create dendritic cells, and then given back to the person. This very specialized vaccine then helps the body fight prostate cancer. This policy describes when this type of immunotherapy may be approved for prostate cancer.
Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered.
Therapy Medical Necessity
Sipuleucel-T therapy Sipuleucel-T therapy may be considered medically necessary in the treatment of asymptomatic or minimally symptomatic, androgen-independent (castration-resistant) metastatic prostate cancer.
Note: Provenge® is the brand or trade name for sipuleucel-T.
Sipuleucel-T therapy Sipuleucel-T therapy is considered investigational in all other situations, including but not limited to: * Treatment of hormone-responsive prostate cancer * Treatment of moderate to severe symptomatic metastatic
prostate cancer * Treatment of visceral (liver, lung, or brain) metastases
The patient’s medical records submitted for review for all conditions should document that medical necessity criteria are met. The record should include clinical documentation of all of the following: * Patient has metastatic prostate cancer that is castrate-resistant (does not respond to hormone
treatment) * Patient is asymptomatic or minimally symptomatic * Patient has no liver, lung, or brain metastases
Sipuleucel-T (Provenge) is a class of therapeutic agent used to treat symptomatic castrationresistant, metastatic prostate cancer. The agent comprises specially treated dendritic cells obtained from the patient through leukapheresis. The cells are then exposed in vitro to proteins that contain prostate antigens and immunologic-stimulating factors and reinfused into the patient. The proposed mechanism of action is that treatment stimulates the patient’s own immune system to resist cancer spread.
Prostate cancer is the second leading cause of cancer-related deaths among American men, with an estimated incidence of 164,690 cases and an estimated number of 29,430 deaths in 2018.
In most cases, prostate cancer is diagnosed at a localized stage and is treated with prostatectomy or radiotherapy. However, some patients are diagnosed with metastatic disease or recurrent disease after treatment of localized disease.
Androgen ablation is the standard treatment for metastatic or recurrent disease. Most patients who survive long enough eventually develop androgen-independent (castration-resistant) prostate cancer. At this stage of metastatic disease, docetaxel, a chemotherapeutic agent, has demonstrated a survival benefit of 1.9 to 2.4 months in randomized clinical trials.
Chemotherapy with docetaxel causes adverse effects in large proportions of patients, including alopecia, fatigue, neutropenia, neuropathy, and other symptoms. Trials evaluating docetaxel included both asymptomatic and symptomatic patients, and results have suggested a survival benefit for both groups. Because of the burden of treatment and its adverse effects, most patients therefore defer docetaxel treatment until cancer recurrence is symptomatic.
Cancer immunotherapy has been investigated as a treatment that could be instituted at the point of detection of androgen-independent metastatic disease before significant symptomatic manifestations have occurred. The quantity of cancer cells in the patient during this time is thought to be relatively low, and it is thought that an effective immune response to the cancer during this interval could effectively delay or prevent progression. Such a delay could allow a course of effective chemotherapy, such as docetaxel, to be deferred or delayed until necessary, thus providing an overall survival benefit.
Summary of Evidence
For individuals who have asymptomatic or minimally symptomatic metastatic castrationresistant prostate cancer who receive sipuleucel-T (Provenge), the evidence includes 3 randomized controlled trials (RCTs) and a systematic review of these RCTs. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related morbidity. The 2 earlier RCTs of sipuleucel-T were not specifically designed to demonstrate a difference in overall mortality but did show a survival difference. The third RCT, which was designed to demonstrate a mortality difference, showed a similar improvement in overall survival. All 3 studies were consistent in demonstrating that sipuleucel-T does not delay time to measureable progression of disease. A meta-analysis of the 3 RCTs found significantly improved overall survival, but not time to progression, with sipuleucel-T compared with placebo. Serious adverse events did not increase in the sipuleucel-T group. However, the available data suggested, but did not confirm, an increase in stroke risk; this risk is being evaluated in a postmarketing study. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.
For individuals who have nonmetastatic androgen-dependent prostate cancer who receive sipuleucel-T (Provenge), the evidence includes an RCT. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related morbidity. The RCT did not find a statistically significant difference between sipuleucel-T and a control in time to biochemical failure. The RCT was not designed to evaluate the impact of sipuleucel-T on mortality. The evidence is insufficient to determine the effects of the technology on health outcomes.
Medicare National Coverage
The Centers for Medicare & Medicaid Services released a national coverage determination in 2011 approving sipuleucel-T for treatment of asymptomatic or minimally symptomatic castrateresistant prostate cancer.
Coverage for off-label indications was left to the discretion of local Medicare administrative contractors.
In 2010, the U.S. Food and Drug Administration approved Provenge® (sipuleucel-T; Dendreon Corp., now Sanpower) under a Biologics Licensing Application for “the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.”
Approval was contingent on the manufacturer conducting a postmarketing study, based on a registry design, to assess the risk of cerebrovascular events in 1500 men with prostate cancer who receive sipuleucel-T.