Lung cancer is one of the most common neoplasms in Brazil and has a high fatality rate. The Brazilian National Cancer Institute (INCA) estimates about 30,000 new cases annually between 2020 and 2022.
In recent decades, the treatment of advanced non-small cell lung cancer (NSCLC) has greatly improved with the development of targeted therapies and immunotherapy (IO). Population studies have already detected an improvement in patient survival,
In this context of effectiveness and increasing costs, studies of health technology assessments (HTA) are increasingly necessary. These studies are important to correlate the clinical benefit of new treatments with the respective incremental cost.
Although RCTs are considered strong scientific evidence, the population included in RCTs does not faithfully represent the real-world population due to the strict inclusion criteria of these studies.
In this sense, there is a growing interest in real-world evidence (RWE) assessing the effectiveness of new technologies in a non-selected population and correlating it with RCT data.
This is a retrospective study that extracted a patient-level data from the Oncoclinicas database. Oncoclinicas is an oncology group present in 11 out of 27 Brazilian federative units and its database is demographically and geographically diverse. The authors randomly selected the de-identified data from 50 patients. The number of patients included was arbitrarily defined. The inclusion criteria were patients aged ≥18 years, confirmed histological diagnosis of non-small cell lung cancer (NSCLC) and at least one systemic treatment performed at Oncoclinicas from 2018 to 2019. The study included patients from stage I to stage IV respecting the Brazilian epidemiological proportion.
All data was de-identified before analysis and the study was approved by the Institutional Review Board with waiver of patient consent (CAAE: 32483720.7.0000.5134). The data lake used in this study does not include clinical and demographic information being focused on clinical outcomes that will be specified in the next section.
The primary endpoint of the study is the average cost of treatment according to the disease stage. The cost analysis considered only direct costs from antineoplastic drugs acquisition retrieved from the reference table of the Brazilian Drug Market Regulation Chamber assessed in July 2021. All costs were converted from Brazilian Reais to US Dollars using an exchange rate of 5.12. The authors considered the Time to Next Treatment (TTnT) as the treatment duration. The TTnT was established as the time from the first record of the treatment until the last record of the same therapy.
Secondary endpoints were the average cost of each line of treatment among patients with advanced disease, the percentage of this amount that was related to IO acquisition and overall survival (OS), defined as the time from the index date until the last follow-up or death. All patients without a follow-up record were censored in the OS analysis.
Patients with advanced NSCLC that received any approved IO (pembrolizumab or nivolumab or atezolizumab) in monotherapy or combined with chemotherapy were divided into two groups: IO at first-line and IO at second-line or beyond. The authors assessed the TTnT and OS of each group. Finally, the study assessed the cost-effectiveness of IO at first-line versus IO at second-line in order to find the best treatment sequencing in terms of RWD pharmacoeconomic.
The average costs of treatment according to the disease stage were analyzed through the Kruskal-Wallis test. The average costs of each line of treatment among patients with advanced disease were assessed through the Friedman variance analysis.
The TTnT and OS for IO at first-line versus IO at second-line were estimated using the Kaplan-Meier method and compared using the log rank test.
The cost-effectiveness of IO at first-line versus IO at second-line was presented as the Incremental Cost Effectiveness Ratio (ICER) per Quality-Adjusted Life Years (QALY). The authors considered four possible health states (alive at first-line, alive at second-line, alive after progression and died) and retrieved each health states’ utility from literature.(101 The time expended in each health state was retrieved from the mean survival at the Kaplan Meier curve.
The study included 4 patients with early-stage NSCLC (stage I and II), 10 patients with locally advanced NSCLC (stage III) and 36 patients with advanced NSCLC (stage IV). The average costs of treatment for each disease stage were respectively US$30,040, US$52,162, and US$95,607 (p=0.071).
Considering only patients with advanced NSCLC, the average costs for each treatment line were US$64,927 for first-line, US$54,657 for second-line, and US$20,112 for third-line (p=0.115). In terms of IO exposure, the average cost of the entire treatment was US$116,623 among patients treated with IO regimen at first-line, US$112,967 at second-line, US$37,279 at third-line, and US$62,321 among patients that have never received IO, with the IO acquisition cost representing respectively 80%, 75%, 17%, and 0% of all these costs.
The median TTnT was 6.9 months for patients treated with IO at first-line and 3.5 months for patients that did not receive IO at first-line (p=0.073). Considering the TTnT of the first and second-line combined, the median time was 10.6 months for patients treated with IO at first-line and 9.3 months for patients treated with IO at second-line (p=0.643). The median OS were 17.1 months and 18.5 months, respectively (p=0.979).
The utility estimated for IO at first-line was 1.16 QALY and 0.97 QALY for IO at second-line. The ICER of IO at first-line compared to IO at second-line was US$19,240. The
| IO at 1st Line | IO at 2nd Line | Utilities | |
|---|---|---|---|
| Total Costs | $ 116,623 | $ 112,967 | - |
| Mean TTnT 1st Line | 12.5 months | 4.2 months | 0.71 |
| Mean TTnT 2nd Line | 2.3 months | 6.8 months | 0.67 |
| Mean PPS | 5.8 months | 6.9 months | 0.59 |
| QALY | 1.16 | 0.97 | |
| ICER | $ 19,240 | Reference |
TTnT: Time to next treatment;PPS: Post-progression survival; QALY: Quality-adjusted life years; ICER: Incremental. Cost-Effective- ness Ratio.
The increased cost of anticancer therapies threatens the sustainability of health systems and, consequently, patients’ access to the best available treatment. However, a large part of the data regarding the costs of new treatments comes from extrapolation of data from randomized clinical trials that present a population profile that is different from the profile of patients in clinical practice.
In this study, it was used a distribution of patients by stage according to national epidemiological data and an evaluation of the average cost per patient treated was performed considering the acquisition of all anticancer therapies throughout the patient’s journey. As expected, the average cost per patient was higher as more advanced the cancer stage. In addition, patients diagnosed with advanced NSCLC treated with IO had an even higher average cost compared to patients who did not receive IO.
Although the average cost per patient with advanced NSCLC was high, it was lower than the expected average value considering the standard therapies available in the country. In a study presented at the World Conference on Lung Cancer in 2020, Silveira et al. (2021),
Despite the clinical and demographic differences between patients in this study and patients enrolled in RCTs, considering patients treated with first line IO, it was observed similar clinical outcomes in terms of OS. However, this study was not developed with the specific objective of evaluating the OS of patients and all analyses in this regard require caution.
The limitation regarding the small number of individuals included limits not only the analysis of OS, but of all other outcomes. Furthermore, retrospective studies have statistical limitations that may decrease the accuracy of pharmacoeconomic analyses. The risk of confounding bias from RWD is the most mentioned limitation in the literature and include the clinical practice of selecting patient profiles for certain approaches that would not be chosen randomly, as they would be in RCTs.
Furthermore, even with the improvement of Big Data in the healthcare area and the possibility of collecting and analyzing a large volume of information from different sources, the risk of losing data in a database such as the one used for this study persists.
A pharmacoeconomic analysis needs to collect and include as much information as possible to reduce uncertainty regarding its outcome. In this sense, the unavailability of data led to the non-inclusion of surgery and radiotherapy costs in the initial cases as well as indirect costs, causing a limitation in this study. In addition, the unavailability of data regarding the occurrence of adverse events represents another limitation for the cost-effectiveness analysis.
Nevertheless, the finding of first-line IO cost-effectiveness of compared to second-line is consistent with other previously published studies that considered RCT data for pharmacoeconomic analysis.
The cost of treating NSCLC is higher as more advanced is the diagnosis of the neoplasm. Considering only patients diagnosed with advanced NSCLC, the cost is higher when the patient has received immunotherapy, and the cost of acquiring this technology represents a major part of the total cost of patient treatment, regardless of whether the IO is performed in the first or second line. Treatment with first-line IO was cost-effective compared to second-line IO.
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Journal: Brazilian Journal of Oncology
DOI: 10.1055/s-00059887
e-issn: 2526-8732
Publisher: Thieme Revinter Publicações Ltda.
Publisher address: Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
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