Drug Profiles

Evidence-Based Oncology, February, Volume 18, Issue SP1

To help oncology providers better understand drug mechanisms of action, and the economic implications of their use.

Nab-Paclitaxel (Abraxane)

Nab-paclitaxel (Abraxane) is an alternative form of the drug where paclitaxel is bound to albumin nanoparticles.

It is an antimicrotubule agent. These work to inhibit the microtubule structures, a part of the cell’s machinery for replicating itself. Inhibition of these structures ultimately results in cell death.

Paclitaxel usually requires solvents to dissolve it before the medication can be administered. When bound to albumin, it dissolves more readily, negating the need for irritating solvents. This means that the medication can be injected more quickly than the non-bound version. There are also indications that the nab-paclitaxel version may preferentially enter the cell.1,2

Nab-paclitaxel is indicated for use in the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.3

The economic impact of nab-paclitaxel has been mixed. Dranitsaris and colleagues looked at clinical and safety data comparing it with docetaxel and noted that nab-paclitaxel had the lowest incidence of grade 3-4 toxicity and lower overall costs of managing the toxic effects. When they used the median number of cycles given and the cost effects of the toxicity, overall cost for nab-paclitaxel was $15,105 compared with $15,268 for docetaxel and $3357 for paclitaxel. However, the incremental cost per quality-adjusted life-year (QALY) gained was more favorable for nab-paclitaxel than docetaxel ($56,800 vs $739,600).4

Another study by the same group compared nab-paclitaxel weekly or every 3 weeks with a standard regimen of docetaxel. Patients getting nab-paclitaxel 100 mg/m2 weekly and 300 mg/m2 every 3 weeks had average costs comparable to the docetaxel arm. Those administered nab-paclitaxel 150 mg/m2 weekly had significantly higher overall costs, but also had a significant improvement in progression-free survival. Relative to docetaxel, the incremental costs per progression-free year were £5660, £31,800, and £9900 for the 100 mg/m2 weekly, 150 mg/m2 weekly, and 300 mg/m2 every 3 weeks dosing, respectively.5

Lenalidomide (Revlimid)

Lenalidomide (Revlimid) in combination with dexamethasone is indicated for the treatment of multiple myeloma (MM) patients who have received at least 1 prior therapy.

How lenalidomide works is not well understood. Experiments have demonstrated that lenalidomide inhibits the growth of cells derived from patients with multiple myeloma in vitro. It has been shown to inhibit the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha. Lenalidomide also inhibited the expression of cycoloxygenase-2 (COX-2) but not COX-1 in vitro.6

A study by Fullerton et al assessed resource utilization in MM associated with 4 approved therapies. They included single-agent bortezomib, bortezomib with pegylated liposomal doxorubicin, thalidomide plus dexamethasone, and lenalidomide plus dexamethasone in their models.

The costs in all models were primarily driven by the direct expenditures for the drugs. The $64,806 cost for lenalidomide with dexamethasone was a 1.7-fold increase over the combination including thalidomide, and a 1.9-fold increase over drug costs for the bortezomib/ doxorubicin combination.

Adding associated medical costs to the model, lenalidomide/dexamethasone represented a cost savings compared with the other regimens. The total cost, including prophylaxis for deep vein thrombosis and pulmonary embolism, was 1½ times that seen in either the thalidomide/dexamethasone or the bortezomib/doxorubicin combination.7

A discrete event simulation model was used to estimate long-term health and cost results of lenalidomide plus dexamethasone versus dexamethasone alone in patients with MM who had received either 1 or 2 or more prior rounds of therapy.

In those with just 1 prior therapy, lenalidomide with dexamethasone was associated with improvements in both survival and QALYs when compared with dexamethasone alone. They equated this to £20,617 per life-year gained and £28,943 in QALYs gained in those patients who received lenalidomide.

When the group with 2 or more previous therapies was assessed, similar results were seen. The incremental cost of the combination was £19,218 per life-year gained and £28,184 per incremental QALY gained.8

Ipilimumab (Yervoy)

Ipilimumab (Yervoy) is indicated for use in melanoma that has metastized or cannot be removed by surgery. It is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).

Blockade of CTLA-4 augments T-cell activation and proliferation. The mechanism of action of ipilimumab in patients with melanoma is indirect, possibly through a T-cell mediated anti-tumor immune response.9

Because of its relative newness, having been approved by the FDA in March 2011, the economic impact of ipilimumab is not yet well defined. A Medline search using the drug’s name and the MESH terms “cost-benefit analysis” and “drug cost/statistics and numerical data” found no studies. A more general search using Google was similarly unproductive, returning only a draft report by England’s National Institute for Clinical Excellence (NICE) and a similar one from Ireland’s National Centre for Pharmacoeconomics (NCPE).

NICE tentatively recommended against adding ipilimumab to the National Health System’s coverage. This does not mean that the medication will be banned, just that the governmental program will not pay for treatment.

The Committee concluded that the most plausible cost per year of improved health would fall between £54,000 and £70,000 per QALY gained. They did note that a lack of data on longer-term benefits could result in a significantly higher true incremental cost-effectiveness ratio (ICER).10

The NCPE also completed an economic evaluation of the medication. The Centre looked at a Markov decision analysis indicating a baseline incremental cost per QALY gained with ipilimumab versus best supportive care as €147,899. The incremental cost per life-year gained was €92,443.

A probabilistic sensitivity analysis indicated that the probability of ipilimumab being cost-effective over a willingness to pay range between €20,000 per QALY to €45,000 per QALY was 0%.

The budget impact assessment, based on a cost per dose above €20,000 and an average cost of treatment over 4 cycles, exceeded €85,000. Differing scenarios put the gross budget impact of using the medication between €4.8 million and €7.4 million in 2012. This would have increased between €500,000 and €1.8 million by 2016.

This led the Centre to conclude that there had been a failure “to demonstrate the costeffectiveness of ipilimumab for the treatment of advanced melanoma in adult patients who received prior therapy.”

Because of that, the Centre could not recommend reimbursement at the submitted price.11

1. Desai N, Trien V, Yao Z, et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, AB-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 2006;12:1317-1324.

2. Anon. How Abraxane may help. http://www.abraxane.com/dtc/how-abraxane-may-help.aspx. Accessed November 13, 2011.

3. Abraxis Bioscience. Abraxane Package Insert Revised. http://www.abraxane.com/docs/Abraxane_ PrescribingInformation.pdf. Accessed November 13, 2011.

4. Dranitsaris G, Cottrel W, Spirovski B, et al. Economic analysis of albumin-bound paclitaxel for the treatment of metastatic breast cancer [published online ahead of print November 26, 2008]. J Oncol Pharm Pract. 2009;15(2):67-78.

5. Dranitsaris G, Coleman R, Gradishar W. Nab-paclitaxel weekly or every 3 weeks compared to standard docetaxel as first-line therapy in patients with metastatic breast cancer: an economic analysis of a prospective randomized trial [published online ahead of print June 3, 2009]. Breast Cancer Res Treat. 2010;119(3):717-724.

6. Anon. Revlimid prescribing information. http://www.drugs.com/pro/revlimid.html. Accessed November 13, 2011.

7. Fullerton DSP, Trautman H, Huang H, et al. A budget impact model comparing resource utilization of four approved therapies for multiple myeloma (MM) in the U.S. [abstract]. Blood. 2007;110:3324.

8. Deniz HB, Ishak KJ, Edwards DR, Shearer A, Dale P, Caro JJ. Economic evaluation of lenalidomide for the treatment of multiple myeloma in Wales in patients who have received at least one prior therapy [abstract]. Haematologica. 2008; 93(suppl 1):0804.

9. Anon. Highlights of prescribing information. http://packageinserts.bms.com/pi/pi_yervoy.pdf. Accessed November 13, 2011.

10. National Institute for Clinical Excellence. NICE consults on a new treatment for skin cancer. http://www.nice. org.uk/newsroom/pressrelease /NICEConsultsOnNewTreatmentForSkinCancer.jsp. Accessed November 13, 2011.

11. National Centre For Pharmacoeconomics. Pharmacoeconomic evaluation of Ipilimumab (Yervoy®) for the treatment of advanced (unresectable or metastatic) melanoma in adult patients who have received prior therapy. http://www.ncpe.ie/u_docs/doc_216.pdf. Accessed November 13, 2011.