On March 30, 2011, the Centers for Medicare & Medicaid Services (CMS) announced its highly anticipated proposed national coverage decision concerning the prostate cancer immunotherapy sipuleucel-T (Provenge; Dendreon). The biologic medication (which is often labeled a “vaccine” because of its immunotherapeutic properties but is rather a therapeutic, not a prophylactic, product) was approved by the US Food and Drug Administration (FDA) in April 2010 for the treatment of men with asymptomatic or mildly symptomatic metastatic prostate cancer. According to the CMS proposed decision, Medicare will reimburse payers for the FDA-approved indication for the drug and leave the coverage decision for off-label uses to its contractors.
CMS “proposes that the evidence is adequate to conclude that the use of [the] autologous cellular immunotherapy treatment—sipuleucel-T; Provenge improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication” (www.cms.gov).
With the cost of this therapy estimated at $93,000 per patient, this product, like many recent cancer products, raises yet again the question of value for therapies that extend life by weeks or months (the drug appears to extend life on average by approximately 4 months, although it is possible that in a subset of patients this time could be extended considerably).
On the FDA approval of the drug, CMS instructed the Medicare Evidence Development and Coverage Advisory Committee to review the evidence from clinical trials as part of its coverage determination, an unusual step for CMS, considering the proximity of this process to FDA approval.
Off-Label Use So far no evidence is available to support the use of Provenge for offlabel uses in patients with prostate cancer. In what is considered an unexpected move, CMS has left the coverage decision for off-label use to payers’ discretion.
CMS says that this is in an effort to allow access to the drug to patients in clinical trials that involve off-label uses, with the hope “that unlabeled uses in the near future will take place only in the context of bona fide clinical studies,” discouraging providers from prescribing it independent of clinical trials. “If this turns out to be an overly optimistic viewpoint,” however, CMS may reconsider this strategy to make sure the Medicare coverage “is restricted to uses that are supported by robust evidence.”
Nevertheless, it is quite likely that this decision also signals CMS’s hope that payers will use the same evidence- based criteria to refuse to pay for off-label uses of the drug, again visà- vis its cost and the increasingly limited resources for regional plans. In fact, it can also be argued that in its statement cited above, CMS is sending a message to the company that offlabel uses should be limited to clinical trials only at this point. It may also be sending a message to other developers of oncology products that it would be looking at off-label uses more carefully in the future. Time will tell.
VBCC Perspectives Revisited Commenting on the question of offlabel use after the approval of the drug last year in the October issue of VBCC, Lee Newcomer, MD, VBCC editorial board member and Business Leader of Oncology Services for UnitedHealthcare, said, “Using the therapy for patients who do not meet the precise indications is simply conducting a $93,000 clinical trial with 1 subject.”
A second VBCC editorial member, Yu-Ning Wong, MD, MSCE, Assistant Professor at Fox Chase Cancer Center, noted that “Oncologists are trained to counsel patients about risks and benefits, including treatment-associated survival improvement and toxicities. However…physicians are ill prepared to add the ‘cost and value’ dimension to these discussions.”
Patient Registry to Provide Additional Data After its recent decision, CMS has announced it is “requesting public comments on this proposed determination pursuant to section 1862 (l) of the Act. After considering the public comments, we will make a final determination and issue a final decision memorandum.” CMS is expected to issue its final ruling by June 30, 2011.
In its February 24, 2011, letter to CMS, Dendreon noted it would analyze its patient registry with the goal of providing long-term real-world information for various subgroups of patients. The company expects that many patients in the registry are likely to be Medicare patients, which will present the opportunity “to compare across age-groups.”
The company’s patient registry will also support analysis of whether black men could benefit more than other groups from Provenge. This is in response to comments by CMS of an underrepresentation of black men in clinical trials of this drug (which is not an uncommon situation in clinical trials conducted by many pharmaceutical companies), although the prostate cancer mortality rate among black men is double that of white men
