Clinical and Economic Benefits of Aromatase Inhibitor Therapy in Early-stage Breast Cancer

Stefan Glück; Fariborz Gorouhi


Am J Health Syst Pharm. 2011;68(18):1699-1706. 

In This Article

Economic Impact of Endocrine Therapy

Treatment decisions are based on clinical efficacy. However, the role of economics in the selection of medical interventions is increasing, especially health care systems. This refers not only to the costs incurred but also to the cost per quality-adjusted life-years (QALYs) gained. The financial impact of treating breast cancer includes not only the cost of acquiring drug but also the cost of adverse-event management and other costs (including routine follow-up, treatment of recurrent disease, and cancer death). As illustrated in the National Institute for Health Research cost analysis over a 35-year period and extrapolated from the 68-month analysis of the ATAC trial, 25.8-month analysis of the BIG 1–98 trial, and 37-month analysis of the IES (Figure 2), the mean cost per patient associated with tamoxifen when converted to 2010 dollars was $8,344–$8,895.[33] For anastrozole, letrozole, and exemestane, the mean costs per patient were $13,416, $14,043, and $11,947, respectively. The differences in cost between tamoxifen and the AIs were due largely to the acquisition of anastrozole ($5,433), letrozole ($6,737), and exemestane ($3,842), which were more costly than tamoxifen ($942–$1,002). However, the availability of anastrozole and letrozole in generic formulations is expected to significantly reduce these costs in the United States.

Figure 2.

Cost per patient based on a 35-year analysis of (A) anastrozole monotherapy versus tamoxifen monotherapy, (B) letrozole monotherapy versus tamoxifen monotherapy, and (C) tamoxifen–exemestane (switch to exemestane monotherapy) versus tamoxifen monotherapy. Adapted from reference 33.

Adverse-event management appears to be more costly for tamoxifen (Figure 2), though this represents the smallest fraction of overall cost. The mean cost of managing adverse events ranged from $939 to $1,002 for tamoxifen and was $491 for anastrozole, $524 for letrozole, and $73 for exemestane.[33] However, the cost for individual patients experiencing an adverse event is much greater. For example, when converted to dollars, the mean cost of managing fractures was $702 for the wrist, $2,340 for the proximal humerus, and $9,360 for the hip. In the 68-month analysis of the ATAC trial, 11.0% and 7.7% of patients receiving anastrozole and tamoxifen, respectively, experienced a fracture.[25] In the 25.8-month analysis of the BIG 1–98 trial, fractures occurred in 5.7% and 4.0% of patients treated with letrozole and tamoxifen, respectively.[26]

Other costs, such as the estimated $20,139 mean cost for the last 3 months of terminal care in the IES and $47,392 mean cost for the first year of distant disease management in BIG 1–98 (Table 2), appear to be the greatest financial burden when compared with the cost of drug acquisition and adverse-event management. In a retrospective analysis of patient charges in a large Mid-western health care system, the mean charges incurred by patients with early-stage breast cancer were significantly lower in the 6- and 12-month periods before any recurrent event ($10,715 and $12,344, respectively) compared with a similar period after recurrence ($45,855 and $79,253).[38] Distant recurrence appeared to be the most costly, with mean charges of $57,642 and $104,502 in the 6- and 12-month periods, respectively, after recurrence. Similarly, using data from a large health care system, the mean monthly charges were shown to be highest for distant recurrence ($37,969), followed by locoregional ($10,934) and contralateral ($9,129) recurrences, when calculated for the year immediately after the recurrence.[22] Based on a 35-year analysis, the mean cost per patient for treatment with AIs was higher compared with the cost of tamoxifen (Figure 2). The largest difference in costs was between letrozole and tamoxifen, possibly due to the significantly reduced risk of recurrence at distant sites.

It is important for clinicians to remember that while the acquisition cost was greater for AIs in the studies analyzed, there appeared to be a reduction in downstream costs when compared with those for tamoxifen, manifested mainly through a reduction in disease recurrence.[39] Cost-effectiveness analyses, which assess the difference in costs of therapeutic interventions over a defined period of time in relation to the difference in benefits achieved, are an accepted measure of the overall economic burden of cancer therapy.[40] Benefits are most commonly measured in life-years or QALYs, and ratios are generally expressed as mean incremental cost per QALY (ICQ) gained. Ratios below $50,000–$100,000 (United States and Canada) or the equivalent of $31,200 (United Kingdom) are generally considered to be acceptable thresholds to society, though the origin of these figures remains unclear. Analyses based on disease recurrence over a period of 7.5[34]–35[41] years have demonstrated that the addition of AIs to standard therapy is similarly cost-effective. In the United States, the mean ICQ of switching to exemestane after 3 years of tamoxifen treatment compared with continuing tamoxifen therapy for the remainder of the 5-year treatment period was estimated to be $20,100.[42] The mean ICQ for 5 years of anastrozole was $20,256 compared with 5 years of tamoxifen,[43] and it was $23,743 for 5 years of letrozole compared with tamoxifen.[36] In Canada, mean ICQs have been calculated at $24,185 for switching to exemestane,[34] $28,000 for anastrozole,[41] and $23,662 for letrozole compared with tamoxifen therapy.[37] In the United Kingdom, mean ICQ estimates were $17,828 for anastrozole[39] and $16,191 for letrozole compared with tamoxifen.[39]

While most cost-effectiveness analyses of these drugs, such as the above, are extrapolated from disease-recurrence data, Karnon and Kaursa.[44] evaluated the cost-effectiveness of 5 years of therapy with letrozole versus tamoxifen and 5 years of therapy with anastrozole versus tamoxifen using a survival-based model. Using the 76-month censored analysis for the BIG 1–98 trial and the 100-month ATAC data, the model predicted that letrozole and anastrozole may increase QALY per patient by 0.26 (3 months) and 0.05 (0.5 month), respectively. Results demonstrated a mean cost increase per QALY equivalent to $16,272 associated with letrozole and $66,543 with anastrozole over a 20-year period. When IPCW estimation for the BIG 1–98 trial was utilized instead of the censored analysis, the incremental mean cost per QALY gained for letrozole monotherapy versus tamoxifen was $15,598 or less while that for anastrozole versus tamoxifen was $73,053.[45] Based on these analyses, there appears to be a considerable difference among the nonsteroidal AIs in favor of letrozole.

Anastrozole and letrozole are now off patent. The availability of generic versions of these AIs is expected to greatly affect the cost-effectiveness of therapy. An extension of the analysis discussed above was conducted before the availability of generic letrozole, taking into consideration significant reductions in price, immediately for anastrozole and after one year for letrozole.[44] Assuming a 50% price reduction, the ICQ for letrozole versus tamoxifen would decrease to the equivalent of $8,050 while that for anastrozole versus tamoxifen would decrease to $25,114. If the price is further reduced to 30% of the cost of the brand-name version, the ICQ would be $5,031 for letrozole versus tamoxifen and $5,939 for anastrozole versus tamoxifen.


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