American Society of Clinical Oncology

Clinical OncologyNanoparticle Albumin-Bound Paclitaxel for Metastatic Breast Cancer

Speaker: William J. Gradishar, MD, Associate Professor of Medicine; Director, Breast Oncology; and Director, Fellowship Program, Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Data from a phase III clinical trial were analyzed to compare nanoparticle albumin-bound (nab) paclitaxel (Abraxane™, Abraxis Oncology, a division of American Pharmaceutical Partners, Inc.) with standard Cremophor®-based paclitaxel (CP) (Taxol®, Bristol-Myers Squibb) for the treatment of metastatic breast cancer. The results indicated that nab-pacli-taxel was more efficacious and less costly than CP, yielding a dominant cost-effectiveness strategy, with the potential for generating significant cost savings for payers and providers.
In this randomized trial, the overall response rates were 33% for women taking nab-paclitaxel and 19% for those taking CP. The time to tumor progression was 21.9 weeks with nab-paclitaxel and 16.1 weeks with CP.

A decision-analytical model was constructed to evaluate the cost-effectiveness of this new therapeutic modality from the perspective of providers and payers. Measures included the following:

  • premedication costs
  • administration costs (e.g., nursing, tubing, and ancillary equipment)
  • treatment-failure costs based on typical chemotherapy regimens
  • toxicity management costs associated with taxane therapy, including standards of care, treatment patterns, and drug costs as well as frequency of grade 3 and 4 toxicities from agents

From these data, the investigators determined the cost-effectiveness ratios of treatments and the overall cost derivations.
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With regard to cost derivations, no premedication costs were associated with nab-paclitaxel because no steroid pre-medication or granulocyte-colony stimulating factors were required. The premedication cost per patient receiving CP was $115.50. The cost of chemotherapy per patient was $85.86 for nab-paclitaxel and $311.75 for CP. The cost of managing grade 3 and 4 toxicities was $4,934.70 for nab-paclitaxel and $7,227.57 for CP. The difference was driven primarily by the incidence of neutropenia and leukopenia, and the cost of treatment failure was estimated to be $1,067.34 lower with nab-paclitaxel than with CP. Chemotherapy drug acquisition costs were not included because pricing for nab-paclitaxel was not available at the time of analysis.

As noted earlier, nab-paclitaxel was more effective, with patients having a median time of progression-free survival of 5.06 months in contrast to 3.72 months with CP. Because nab-paclitaxel was more effective and less expensive, incremental cost-effectiveness ratio calculations were not necessary.

Novel Chemotherapeutic Combination for Locally Advanced

Speaker: Jose Baselga, MD, Chairman, Oncology Service, Hospital Vall d’Hebron, Barcelona, Spain.

The combination of temsirolimus (CCI-779, Wyeth Research), a novel targeted mTOR kinase inhibitor, and letrozole (Femara generic, Novartis), a well-known aromatase inhibitor, was well tolerated and effective, when administered on a low-dose schedule, in the treatment of postmenopausal women with locally advanced or metastatic breast cancer. The synergistic effects of the two antitumor agents allowed for decreased doses with fewer adverse drug effects (ADEs).

Researchers enrolled 80 postmenopausal patients into a phase II, three-arm study designed to evaluate two separate doses and schedules of orally administered temsirolimus, combined with letrozole as first-line or second-line therapy, in order to determine its preliminary safety and efficacy, as measured by objective tumor response rates. The women were randomly selected, in a 1:1:1 ratio, to receive the following regimens:

  • a high-dose schedule for oral temsirolimus 25 mg daily or oral temsirolimus 75 mg five days every two weeks plus oral letrozole 2.5 mg daily (six patients in each group)
  • oral daily alone (three patients)

Because temsirolimus toxicity resulted in a dose delay, a dose reduction, or discontinuation of the high doses of this agent, the protocols were amended. Doses were reduced to lower amounts of oral temsirolimus: 10 mg daily or 30 mg five days every three weeks along with oral letrozole 2.5 mg daily (22 patients and 19 patients, respectively) or oral letrozole 2.5 mg daily alone (24 patients).

The low-dose schedules were well tolerated, with few dose delays or reductions occurring. ADEs such as mucositis, asthenia, constipation, headache, rash, vasodilation, and back pain were mainly grade 1 or 2. The preliminary best tumor response data supported the selection of the temsirolimus 30-mg intermittent dose in combination with letrozole. With this combination, the objective response rate was 26%, with one complete response, four partial responses, and disease progression in one patient.

In the group receiving the 10-mg daily dose of temsirolimus plus letrozole canadian, the objective response rate was similar, at 23%, with five partial responses; however, disease progressed in four patients. The remainder of the patients have been in the study for too short a time to evaluate stable disease.

The efficacy of letrozole alone was as expected in this patient population, with an objective response rate of 30%, all partial responses.