The use of adjuvant chemotherapy in EBC has been beneficial to some patients by decreasing tumor recurrence and increasing OS; however, in certain cases, chemotherapy can generate serious adverse events that cause deterioration in the quality of life and substantial increase in health costs(2, 4, 24). Furthermore, in this population, it is typically difficult to determine whether chemotherapy should be administered(35).
Gene expression profiles such as MMP and ODX have established more precisely the prognosis and helped define the benefit of chemotherapy treatment in an individual assessment. This results in the accurate selection patients and avoids unnecessary therapies; however, performing these tests may imply an additional cost (16, 20). These tests are recommended by different clinical practice guidelines, especially for patients with a high clinical risk, and they are often used in Colombian oncology practice (15).
In this study, which was possibly the first in Colombia, we found that performing ODX or MMP is a cost-effective strategy for the health system and generates economic savings. In our model, although we observed an increase in life-years after comparing the performance of standard strategy (4.36) with that of MMP (4.34) or ODX (4.33), these results are at the expense of deterioration in the quality of life that can be attributed to chemotherapy treatment, resulting in a benefit in terms of QALY that favors MMP or ODX (0.03 and 0.05, respectively). Despite the possibility of these differences in improvements in both life-year and QALY not being statistically or clinically significant, the capability of MMP or ODX tests to better select patients for chemotherapy results in the reduction of the cost of chemotherapy treatment. The incremental NMB for ODX is $2,741 and that for MMP is $771, indicating that genomic profiling using these tests generates an economic surplus compared with the standard strategy in the WTP threshold defined for Colombia as 1 GDP per capita for the QALY analysis. In this case, the cost to obtain the benefit is less than the maximum amount that the Colombian NHS would consider paying for this benefit. In the sensitivity analysis, MMP could not be considered economically acceptable only when the costs of adjuvant chemotherapy were <$274 per month of treatment.
Notably, even when the system is not willing to pay any cost for this benefit, i.e., with a WTP threshold of $0, both tests are cost-effective (incremental NMB for ODX at $2,446 and incremental NMB for MMP at $570).
From the perspective of the Colombian NHS, for a WTP of 1 GDP per capita, there is a 95.5% and 70.2% probability that ODX and MMP tests will be cost-effective, respectively. Importantly, even with a WPT of COP 0, the probability that the tests are cost-effective is high, especially for one of the tests (99.1% for ODX and 66.7% for MMP).
Our results are in agreement with those reported previously in the literature. A cost-effectiveness study of the genomic profile for breast cancer conducted in Canada that included information from the TAILORx(20) and MINDACT (16) trials showed that the genomic profiling of breast cancer patients using ODX or MMP tests is a cost-effective strategy below the threshold of WTP defined for this study when compared with the standard management, i.e., the absence of any test. In this analysis, ODX has a 89.2% probability and MMP has 89.2% probability of being cost-effective for a WTP threshold of Canadian dollar 50,000 (36).
Several systematic reviews have concluded that performing the genomic profile in EBC to define adjuvant chemotherapy treatment is a cost-effective strategy (37–39). However, other analyses have shown that this finding is not consistent in all population subgroups and that ODX genomic profile is cost-effective when performed in a high–clinical risk population and not in a low–clinical risk population. A cost-effectiveness study conducted by the UK National Institute for Excellence in Health and Care found that neither ODX nor MMP was cost-effective from the perspective of the UK health system(40). No predictive role of the benefit of chemotherapy was considered for ODX or MMP. Notably, at the time of performing this analysis, the results of the TAILORx trial were unknown, which demonstrated the ability of ODX to establish not only prognosis but also the benefit of adjuvant chemotherapy(20). When the predictive role of ODX to establish the benefit of adjuvant chemotherapy was included, this test was cost-effective, particularly for patients with high clinical risk (for this study defined as the subgroup with NPI > 3.4) a finding similar of ours(40). In MMP, despite the results of the MINDACT trial (16), this test was not cost-effective(40).
Several cost-effectiveness studies have not considered this analysis for clinical risk subgroups, which could favor the new test as cost-effective, and for this reason, the incorporation of clinical characteristics into the cost-effectiveness models is recommended(41). In contrast, the performance of MMP is only recommended in patients with high clinical risk, and the combination of these clinical criteria with ODX result can increase its prognostic capacity(42, 43). Only patients with high-risk clinical criteria were included in our model, which is a conservative strategy, demonstrating that performing MMP or ODX in this population is a cost-effective strategy. Hall et al. found results similar to ours in the United Kingdom when they used a model that also included patients with high clinical risk with lymph node involvement (31). In addition to MMP and ODX, other tests such as PAM-50 (Prosigna™), MammaTyper™, IHC4, and IHC4-AQUA™ (NexCourseBreast™) were also evaluated by Hall et al. and found an 86% probability that gene expression profiles are cost-effective in defining the need for adjuvant chemotherapy in patients with EBC (31).
In our study, when two ODX tests were compared, and they were more cost-effective than MMP with an incremental NMB of $2,050 and 99% probability of being more cost-effective. Our findings suggest that to achieve results similar to those of ODX test, the costs of MMP test should be lower.
Most cost-effectiveness studies have assumed that the relative risk reduction (RRR) for distant recurrence attributed to chemotherapy varies according to different genomic risk groups, i.e., the RRR is 0 for patients with low genomic risk and higher for those with high genomic risk. These assumptions make genomic testing more cost-effective because it can better establish the magnitude of chemotherapy benefit than the traditional clinical criteria. However, the predictive values of these tests, for these cost-effectiveness studies, were based on limited information based on retrospective analysis (44, 45). In our model, we considered information from prospective studies with a significant number of patients, in which the predictive role of the tests has been demonstrated, particularly for ODX (16, 20).
Our study has several limitations. Foremost, we were not able to identify QALY for our population. Despite being a methodological limitation, some guidelines recommend QALY as an outcome measure because this measure more comprehensively evaluates health outcomes (17). For our case, it is essential to establish the effect of chemotherapy on the quality of life, and according to our results, they are significant when evaluated from this perspective. Despite these limitations, variations that could exist in the valuations of the utilities do not alter our results, as evidenced by the DSA. Although there could be variations in utilities among different populations, these variations, regardless of their significance, did not seem to affect our results. However, it is essential to assess QALYs and the utilities for the Colombian population, so that more accurate cost-effective evaluations can be performed in different scenarios, especially in those closely related to the quality of life, such as in oncological diseases. As shown in our analysis, if measures of effectiveness, such as years of life, are analyzed, a treatment or strategy will be considered not cost-effective, as its effect on the quality of life will be ignored. Another limitation of our study is the 5-year time horizon, which is relatively short when compared with that used by other cost-effectiveness studies. This time horizon includes the main relevant outcomes, especially the secondary event associated with chemotherapy that was considered in our model, which was febrile neutropenia. In this regard, our model is conservative, as it does not account for other adverse events attributable to chemotherapy, such as heart failure or the development of secondary malignancies. These adverse events have a negative effect on the quality of life, risk of death, and increased health costs. Furthermore, by the time of the analysis, only 5-year follow-up data were available for one of the trials used (16), and we preferred to not include survival assumptions in our model.
Considering that genomic profiling using ODX and MMP tests is a cost-effective and cost-saving strategy, establishing the budget effect of these tests could be important to define whether they can be included in Colombia’s health benefit plan.