Two Adjuvant Treatments for Breast Cancer Earn Their Keep

TORONTO, June 26 -- Two well-accepted adjuvant therapies for early breast cancer proved cost-effective for improving survival, according to a pair of studies.
Both exemestane (Aromasin) and trastuzumab (Herceptin) have been proven effective in adjuvant breast cancer therapy, and the drugs are included in professional treatment guidelines.
But given their cost, one set of researchers in Canada and another in the U.S. evaluated the cost-effectiveness of the drugs, and reported their findings online in Cancer, with publication in the Aug. 1 issue of the journal.
Each study, one for each drug, found a low projected lifetime cost under $30,000 per life-year gained, adjusted for quality of life.
In the Canadian study of postmenopausal women with estrogen-receptor-positive breast cancer, switching to adjuvant exemestane, an aromatase inhibitor, after two or three years of tamoxifen (Nolvadex) extended disease-free survival at a minimal cost of under $3,000 per patient per year over 7.5 years, Nicole Mittmann, M.Sc., Ph.D., of the University of Toronto, and colleagues found.
Their analysis used a hypothetical cohort of postmenopausal women from the recent Intergroup Exemestane Study (IES), which found a survival benefit for switching to exemestane.
Disease progression and hazard ratios for recurrence and survival were determined from IES datasets, the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, and from published literature.
Cost-effectiveness, from a government-payer perspective, was measured not only in life years gained but was adjusted for gain in quality of life. The combination was expressed as quality-adjusted life years gained.
Five years after completing adjuvant therapy (a total of 7.5 years) a tamoxifen-exemestane adjuvant protocol improved absolute disease-free survival by 2.6% (80.9% versus 78% for tamoxifen alone).
Compared with continued tamoxifen, sequential therapy with tamoxifen and exemestane increased the total discounted medical costs in Canadian dollars by $2,889 per patient over 7.5 years.
Cost savings in the exemestane group for reduced cancer recurrence were $1,680 per person and for other cancers, $221 per person.
The incremental cost-effectiveness ratio for exemestane was $28,119 per life year gained.
Calculated as the quality-adjusted life year gained, the incremental cost-utility ratio was $24,185.
This was well below the estimated threshold of $50,000 Canadian per quality-adjusted life year gained, the researchers reported.
A limitation of the study, the researchers noted, is that the analysis was based on data from a clinical trial, which may not reflect real-world practice.
This study reinforces the recent recommendation in Canada to fund the sequential use of tamoxifen and exemestane as a standard of care for postmenopausal women with ER-positive breast cancer or breast cancer of unknown ER status, Dr. Mittmann and her colleagues concluded.
In the second study of breast cancer patients positive for human epidermal growth factor receptor 2 (HER2-positive), adding trastuzumab proved cost-effective over an estimated lifetime, Louis P. Garrison Jr., Ph.D., of the University of Washington in Seattle, and colleagues reported.
From a payer-perspective, trastuzumab, a monoclonal antibody that targets HER2, was estimated to be cost-effective at a projected low lifetime cost of $26,417 per quality-adjusted life year gained, the researchers said.
Long-term survival and outcome data based on a joint analysis of two major clinical trials were projected from a Markov model with four health states (treatment, disease-free, distant recurrence, and death).
Heathcare resource costs were based on 2006 Medicare reimbursement rates and other published data.
The researchers estimated the cost for a 50-year old woman on the basis of trial results through four years and estimates of long-term recurrence and death derived from a meta-analysis of the trials.
From six years onward, rates of recurrence and death were assumed to be the same in both the trastuzumab and standard chemotherapy-only arms.
Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year gained was a low $26,417 (range, $9,104 to $69,340 under sensitivity analysis), the researchers reported.
The incremental lifetime cost was $44,923, while the projected life expectancy was three years longer for patients who received trastuzumab (19.4 years versus 16.4 years).
Over 20 years, the projected cost of adding trastuzumab to chemotherapy was $34,201 per quality-adjusted life year gained.
Key drivers of cost effectiveness were price of the drug and the probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis, the researchers reported.
The low $26,416 lifetime projection was driven by substantial absolute advantages in clinical outcomes observed with trastuzumab in the joint analysis of the two major trials. These included a 16-percentage-point improvement in freedom from distant recurrence and a 4.8-point improvement in overall survival at four years, the researchers said.
Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost-effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments, the researchers concluded.
Dr. Mittmann and co-author Nancy A. Risebrough, B.A., reported receiving unrestricted funding from Pfizer Canada, Inc., for the economic evaluation of exemestane. The study was supported by a grant from Pfizer Inc. The researchers also thanked two Pfizer employees for their detailed review of this article, which was prepared with the assistance of BioMedCom Consultants Inc. of Montreal.
Primary source: CancerSource reference: Risebrough NA, et al "Cost-effectiveness of Switching to Exemestane Versus Continued Tamoxifen as Adjuvant Therapy for Postmenopausal Women With Primary Breast Cancer" Cancer 2007; DOI: 10.1002/cncr.22824. Additional source: CancerSource reference: Garrison Jr. LP. Et al "Cost-effectiveness Analysis of Trastuzumab in the Adjuvant Setting for Treatment of HER-2-Positive Breast Cancer" Cancer 2007; DOI: 10.1002/cncr.22806.