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Reimbursement and Managed Care News for October 207

OBTN, October 2007, Volume 1, Issue 8

Topics covered in this issue include: 1) Bad News for Health Plans: MRIs Gain in Breast Cancer Detection 2) Do Terminally Ill Patients Have a Right to Receive Unproven Drugs? 3) Benefits of HPV Vaccine Still Unclear, but Time Will Tell 4) Updated Kidney Cancer Guidelines Focus on Medication Revisions 5) Simultaneous, not Sequential, Abl Kinase Inhibitors for Chronic Myelogenous Leukemia 6) The Cost Effectiveness of Proton Beam Radiation Use in Prostate Cancer 7) Can We Stem the Waste of Unused Trastuzumab?

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Bad News for Health Plans: MRIs Gain in Breast Cancer Detection

A study from the University of Washington Medical Center, Seattle, has confirmed what the American Cancer Society already recommends: In women at high risk, magnetic resonance imaging (MRI) better detects breast cancer than mammography or ultrasound alone. The problem is that MRI costs more than the other two methods, and with the weight of the guideline behind it, managed care plans will be hard pressed to deny the prescribed imaging.

This study of 171 women (avg age, 46 yr) at high risk but without symptoms revealed six tumors, all of them caught by MRI. Only two were recognized by mammography, and one was identified by ultrasound. A woman at high risk was defined as possessing either the BRCA 1 or 2 genes or with a strong family history of breast cancer.

Although the percentage of premenopausal women at high risk is estimated at 2%, MRI might also be utilized in the many women in whom mammography is not helpful because of high-density breast tissue, for example. Furthermore, the researchers believe that MRI may be useful in annual screening exams for postmenopausal women and recommend that studies be undertaken to determine if this indeed the case. If so, the health plans may have an additional significant, routine budgetary expense.

A separate study, utilizing the databases of multiple managed care organizations, found that in patients older than 65 years who are breast cancer survivors, more frequent screening may be beneficial. The investigators found that “each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality.” A greater problem may be that not all older patients who are breast cancer survivors are receiving annual mammograms.

Lash TL, Fox MP, Buist DSM, et al: Mammography surveillance and mortality in older breast cancer survivors

2007;25:3001-3006.

Lehman CD, Isaacs C, Schnall MD, et al: Cancer yield of mammography, MRI, and ultrasound in high-risk women: Prospective multi-institution breast cancer screening study

2007;244:381-388.

. J Clin Oncol . Radiology

Do Terminally Ill Patients Have a Right to Receive Unproven Drugs?

Health plans and other payers have struggled for many years with the question of whether they should have to pay for investigational treatments for patients with terminal disorders, such as advanced metastatic cancer. The Fox v. HealthNet case in the early 1990s cast a pall on the managed care industry, when a health plan was forced to pay an $87 million jury award to the survivors of a patient with advanced breast cancer who was denied payment for a bone marrow transplant.

A federal appeals court has handed down a decision that will help managed care plans and insurers defend against lawsuits in these cases. The Court’s ruling, that patients who are terminally ill do not have the Constitutional right to expect access to unapproved therapies that may be potentially lifesaving. The justices indicated that this was a problem with the Food and Drug Administration’s approval system, and that it was up to Congress to change it.

In this case, Abigail Alliance v. McClellan, a suit was brought against the Food and Drug Administration and the Department of Health and Human Services for not providing access to investigational drugs for the terminally ill. Abigail Burroughs was a 21- year-old woman who died in 2001 and was denied the use of two investigational oncology agents recommended by the oncologist (and which were later approved by the FDA). If the FDA approves the medication, then insurers will have far greater difficulty denying access to it.

The central issue was whether the basic rights granted under the Fifth Amendment actually included the right to potentially lifesaving investigational drugs. The Court voted 8-2 that it did not.

Savage DG: Court denies test drugs to dying patients.

August 8, 2007.

Los Angeles Times

Benefits of HPV Vaccine Still Unclear, but Time Will Tell

States continue to ponder the issue of making vaccination for the human papilloma virus (HPV) mandatory for girls, but researchers have not yet reached a conclusion on the overall societal benefit of the vaccine. Canadian population health scientists have contributed to the discussion by performing an economic analysis.

Assuming that the HPV vaccine is given to girls at 12 years of age, and it has an efficacy of 95% that does not wane over time, the number of girls who need to be vaccinated to prevent one episode of genital warts is eight. The number needed to be vaccinated to prevent one case of cervical cancer is 324, according to their study.

However, by varying their assumptions, the case for mandatory vaccination becomes less clear, assert these authors from the Center Hospital of the University of Quebec. For instance, if the vaccine protection wanes at a rate of 3% per year, the predicted numbers needed to vaccinate to prevent a case of genital warts or cervical cancer increase to 14 and 9,080, respectively. The use of a booster dose would help a great deal in this measure, lowering both figures to nine and 480, respectively.

The researchers found that varying the point efficacy of the vaccine between 70% and 100% did not greatly alter the results. The Figure illustrates a sensitivity analysis for the prevention of cervical cancer, showing that the most dramatic shiftin results was clearly associated with the duration of vaccine protection, which at this time is not well understood.

Brisson M, Van de Velde N, De Wals P, et al: Estimating the number needed to vaccinate to prevent diseases and death related to human papilloma virus infection

2007;177:464-468.

. CMAJ

Updated Kidney Cancer Guidelines Focus on Medication Revisions

When making formulary decisions on cancer or other life-threatening disorders, managed care organizations will tend to rely on professional practice guidelines, such as those developed by the National Comprehensive Cancer Network (NCCN) or the National Kidney Foundation. In doing so, they tap into highly regarded medical judgment, which keeps them on a good legal foundation should access questions arise.

The FDA approved temsirolimus for the treatment of patients with recurrent or inoperable stage IV renal cancer (with clear or non—clear cell histology). The drug also was found to have benefit in a recent multicenter, randomized clinical trial of over 600 patients. The NCCN has revised its kidney cancer guidelines to reflect the accepted use of temsirolimus as a first-line therapy in this patient population. It is listed as a category 1 recommendation for patients with poor prognosis and clear-cell histology. The use of temsirolimus is indicated as a category 2A recommendation for patients with non–clear cell histology.

A change in bevacizumab (Avastin) utility is also highlighted in the new guidelines. The results of a trial announced at the 2007 conference of the American Society of Clinical Oncology prompted NCCN to recommend bevacizumab combined with interferon alfa-2a as a first-line choice in patients with inoperable or recurrent stage IV kidney cancer (with predominant clear-cell histology).

The revised guidelines are available at www.nccn.org.

NCCN updates kidney cancer guidelines (press release). Jenkintown, PA,

August 1, 2007.

NCCN,

Simultaneous, not Sequential, Abl Kinase Inhibitors for Chronic Myelogenous Leukemia

It has been well understood that if an Abl kinase inhibitor like imatinib or dasatinib did not produce remission in a patient with chronic myelogenous leukemia (CML), the most likely explanation has been a mutation to the Bcr-Abl oncogene, hindering the effectiveness of the medication. The next step is usually sequential therapy, trying one of the drugs in this class that has not yet been used. Researchers from the United States and Australia report that their small trial may indicate that this is not the best approach.

Journal of Clinical Investigation

They conducted a genetic analysis of 17 consecutive patients with advanced-phase CML who relapsed after sequential treatment with dasatinib after resistance developed with initial imatinib therapy. The investigators found that all of the patients had developed new mutations. Twelve of the mutations were of the T315I genotype. “The fact that all 17 patients acquired new Abl mutations provides evidence that CML cells remain dependent on Bcr-Abl function even after multiple prior anti-Abl therapies and suggests that Bcr-Abl—independent mechanisms of relapse are rare,” write the authors of this article in the .

One of the patients began a trial of combination therapy with imatinib and dasatinib, despite the presence of the T315A mutation (which evolved after a 6-mo response to dasatinib). The patient responded to therapy, with a white blood cell count of less than 1,000/mm3 and a reduction of peripheral blood myeloblasts from 66% to 10%. The response was sustained for at least two months, according to the investigators. They hypothesize that combination therapy restricts the growth of mutation-expressing cells.

It is possible that combination therapy will be necessary for patients who fail sequential Abl-kinase treatment, and the authors question whether this may be optimized if given before resistant mutations arise. If so, managed care plans will have to alter their prior authorization guidelines to allow use of these critical (but relatively costly) therapies to be given at the same time rather than in a sequential manner only. Dasatinib can cost $5,200 per month, and imatinib can cost around $4,000 per month (depending on the dose), according to information from Walgreen’s.

2007 (Aug 16); E-pub ahead of print.

Shah NP, Skaggs BJ, Branford S, et al: Sequential Abl kinase inhibitor therapy selects for compound drug—resistant Bcr-Abl mutations with altered oncogenic potency. J Clin Invest

The Cost Effectiveness of Proton Beam Radiation Use in Prostate Cancer

Compared with state-of-the-art therapy for adenocarcinoma of the prostate, is therapy with high-dose proton-beam radiation cost effective? The answer could be an important factor in whether additional proton- beam devices and facilities are necessary.

Researchers from Fox Chase Cancer Center, Philadelphia, used a Markov decision-tree model, utilizing efficacy, safety, and recurrence information published in the literature. They assumed that using proton-beam technology would allow a higher dose of radiation to be delivered than with conventional intensity-modulated radiation therapy (91.8 cobalt gray equivalents [CGE] vs. 81.0 CGE, respectively). They conducted their analysis using two models—a 60-year-old and a 70- year-old man.

Mean cost of radiation therapy at 15 years

70-year-old*

60-year-old*

Proton Beam Radiation

$63,511

$64,989

Intensity-Modulated Radiation

$36,808

$39,355

Cost-Effectiveness Ratio

$63,578/ QALY

$55,726/ QALY

*Age at time of therapy.QALY= Quality-adjusted lifeyear.

Assuming quality-adjusted survivals of 9.91 quality-adjusted life-years (QALYs) for the younger patient undergoing protonbeam radiation treatment with 9.45 QALYs if he had undergone conventional radiation therapy, and 8.54 and 8.12 QALYs, for the older patient, respectively, protonbeam therapy was deemed cost ineffective for a 15-year period. For the hypothetical 60-year-old patient, the incremental costeffectiveness ratio was $55,726/QALY. For the 70-year-old man, the cost-effectiveness ratio was $63,578/QALY. Both of these figures are greater than the threshold most commonly used of $50,000/QALY and would thus call into question its general use in patients with prostate cancer.

Konski A, Speier W, Hanlon A, et al: Is proton beam therapy cost effective in the treatment of adenocarcinoma of the prostate?

2007;25:3603-3608.

J Clin Oncol

Can We Stem the Waste of Unused Trastuzumab?

Trastuzmab (Herceptin) is heavily utilized throughout the globe as first-line treatment for women with BRCA 1 or 2 positive breast tumors, but a study from Australia confirms that a significant portion of the dispensed medicine goes unused.

Researchers from Sydney followed the care of 1,469 women with metastatic breast cancer who received trastuzumab in the Australian health care system over a 39-month period. Roughly one in seven patients with breast cancer in Australia receive trastuzumab. Using the country’s single-source, universal health plan, the investigators were able track the duration of therapy, extent of drug volume, and cost, including wastage.

They found that 70% of the patients received trastuzumab as combination therapy, and 22% were given the product for off-label uses. Other concerning findings included that the median duration of use of the agent was nearly double that seen in the clinical trials. Perhaps most importantly, they estimated that 24% of all the trastuzumab dispensed was not used (accounting for approximately $17 million [in U.S. dollars] in expenditures for drug purchased but not administered.

The authors of this study believe that optional vial sizes can reduce wastage to around 6% of the total dispensed. They also point to the possibility of alternative administration schedules to more efficiently utilize the medication dispensed.

Pearson S-A, Ringland CL, Ward RL: Trastuzumab and metastatic breast cancer: Trastuzumab use in Australia—monitoring the effect of an expensive medicine access program

2007;25:3688-3693.

. J Clin Oncol