Immune checkpoint inhibitors for the treatment of non-small cell lung cancer: The regulatory journey in Brazil.

BACKGROUND: Recent therapeutic advances such as immune checkpoint inhibitors (ICIs) have impact on the care of non-small cell lung cancer (NSCLC) patients, however, they bring new setbacks for regulatory agencies. OBJECTIVE: To evaluate the regulatory journey of ICIs registered for NSCLC treatment in Brazil and to establish comparisons of Brazilian regulatory agency with the US regulatory agency. METHODS AND DATA SOURCE: Information for each ICI prescribing as well as the date of regulatory approval of the therapeutic indications of interest were collected from the Anvisa and the FDA websites. The search took place on October 2022. KEY FINDINGS: There are only 20 % disagreements on regulatory approvals between Anvisa and FDA. The prioritization review at Anvisa in 2008 has made the regulatory assessment faster. CONCLUSIONS: The results of this study identified a potential improvement in Anvisa's time performance to connect the target established by the legal framework of the sector.

Does it fit in your pocket? economic burden of PD-1 inhibitors' toxicity in the supplementary health system: evidence from Brazil.

BACKGROUND: A full understanding of the economic burden associated with treatment-related adverse events (AEs) can aid estimates of the incremental costs associated with incorporating new technologies and support cost-effective economic modeling in Brazil. In this context, the main objective of this work was to evaluate in a real-life database: (i) the direct medical cost of monitoring the occurrence of AEs (CMO); (ii) the direct medical cost of managing an identified AE (CMN); and (iii) the total direct medical cost of monitoring and managing AEs (TMC), in quarterly periods from 0 to 24 months of the monitoring of cancer patients who used a PD-1 inhibitor from the perspective of the supplementary health system in Brazil. METHODS: This study was conducted from the supplementary health system (SSS) perspective and followed the methodological guidelines related to cost-of-illness studies. A bottom-up (person-based) approach was used to assess the use of health resources to monitor and manage AEs during the use of PD-1 inhibitors, which made it possible to capture differences in the mean frequency of the use of health services with stratification results for different subgroups. As the Brazilian SSS is complex, asymmetric, and fragmented, this study used information from different sources. The methodology was divided into three parts: (i) Data Source: clinical management of AEs; (ii) Microcosting: management of the economic burden of AEs; (iii) Statistical analysis: stratification of results for different subgroups. RESULTS: Analysis of the economic burden of toxicity showed higher CMO costs than CMN in all the periods analyzed. In general, for every BRL 100 on average invested in the TMC of AEs, BRL 95 are used to monitor the occurrence of the AE and only BRL 5 to manage an identified AE. This work also showed that the sociodemographic characteristics of patients, the journey of oncological treatment, and the toxicity profile affect the economic burden related to AE. CONCLUSION: This study provided real-world evidence of the economic burden of AEs associated with the use of PD-1 inhibitors in Brazil. This work also made methodological contributions by evaluating the economic burden of AE of PD-1 inhibitors considering the kinetics of toxicity occurrence and categorizing the costs in terms of CMO, CMN and TMC.

Number needed to treat analysis applied to pembrolizumab plus chemotherapy for first-line treatment of non-squamous non-small cell lung cancer.

AIMS: Considering that healthcare systems' financial resources are limited, we aimed to analyze the number needed to treat (NNT) and cost of preventing an event (COPE) related to drug use from Supplementary Health System (SSS) perspective. METHODS: Data from KEYNOTE-189 (NCT02578680) were considered, comparing pembrolizumab + chemotherapy to chemotherapy alone. A cost-per-responder model was developed considering the 24- and 12-month time horizons for overall survival (OS) and progression-free survival (PFS) endpoints, respectively. Restricted mean survival time (RMST) and restricted mean time-on-treatment (ToT) were determined for NNT and COPE calculation. Costs were reported in American dollars (USD) and reflect those related to drug use. The analysis was conducted for the total indicated population, and an exploratory assessment was carried out for subgroups with different programmed death-ligand 1 (PD-L1) expression levels. RESULTS: Considering PFS data, the overall population NNTRMST to prevent a progression event with pembrolizumab + chemotherapy versus chemotherapy was 2.63 (95%CI: 1.90-4.02) with an estimated COPE of 251,038 USD (95%CI: 181,359-383,717) in the 12-months follow-up. Regarding OS endpoint, overall NNTRMST and COPE were 3.18 (95%CI: 2.20-5.31) and 414,163 (95%CI: 286,528-691,573) USD respectively, in the 24 months follow-up. The PFS NNT was lower with higher levels of PD-L1 expression (1.71, 3.22 and 5.53 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively), while there was no such apparent relationship for OS (3.23, 4.37 and 2.80 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively). The 95%CIs overlapped for PFS and OS NNT across the PD-L1 subgroups. CONCLUSION: The magnitude of benefit of the pembrolizumab combination used for first-line non-small cell lung cancer (NSCLC) treatment to improve survival compared to chemotherapy alone was confirmed. The exploratory analysis from the SSS perspective suggests no differences among the PDL-1 subgroups in terms of clinical benefit or economic impact.

Cutaneous melanoma: cost of illness under Brazilian health system perspectives.

BACKGROUND: The landscape of cutaneous melanoma (CM) diagnosis, staging, prognosis, and treatment has undergone fundamental changes in the past decade. While the benefits of new health resources are recognized, there is a distinct lack of accurate cost-of-illness information to aid healthcare decision makers. METHODS: The cost-of-illness study for CM was conducted from the perspective of two health systems in Brazil: the public health system (Unified Health System, SUS) and the private health system (Health Management Organization, HMO). The study considered the direct medical cost in a bottom-up analysis, using melanoma incidence, knowledge of the disease's progression, and the overall survival rates. The executional costs for the complete healthcare delivery cycle were investigated considering different disease stages and possible clinical course variations. The structural cost was assessed qualitatively considering the health value chain in Brazil. RESULTS: CM represents a critical financial burden in Brazil, and the cost of illness varied according to the health system and by stage at diagnosis. HMO patient costs are approximately 10-fold and 90-fold more than a SUS patient in the early-stage and advanced disease, respectively. Overall, spending on advanced disease patients can be up to 34-fold (SUS) or 270-fold (HMO) higher than that required for the early-stage disease. Given the massive amount of resources spent by the SUS and HMO, significant efforts must be made to improve the health value chain to deliver the right mix of medical care goods and services using available resources. CONCLUSION: The cost-of-illness study for CM has the potential to inform policymakers and decision-makers regarding the economic burden that melanoma impose on a society in terms of the use of health care services, assisting them in making projections of future health care costs and resource allocation decisions. We believe that cost-of-illness analysis from a strategic perspective could be of help in assessing executional costs and be used to support the change in structural costs required for long-term strategies related to the health value chain.

Pembrolizumab plus axitinib and nivolumab plus ipilimumab as first-line treatments of advanced intermediate- or poor-risk renal-cell carcinoma: a number needed to treat analysis from the Brazilian private perspective.

BACKGROUND: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. METHODS: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. RESULTS: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. CONCLUSION: At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.

Concern over cost of and access to cancer treatments: A meta-narrative review of nivolumab and pembrolizumab studies.

BACKGROUND: A better understanding of the modulation of the immune system has resulted in the development of new classes of antitumor agents such as nivolumab and pembrolizumab. Despite the proven effectiveness and tolerability of these new drugs for specific types of cancer, the high cost of treatment has affected their accessibility. OBJECTIVE: The aim of this study is to conduct a meta-narrative review of studies that have addressed the concerns that have been voiced regarding the cost of and access to nivolumab and pembrolizumab in oncology health care. This meta-narrative review attempts to answer the following questions: (1) which papers have considered this broad topic area?; (2) what are the main empirical/theoretical findings?; and (3) what insights can be drawn by combining and comparing findings from different papers? METHODS AND DATA SOURCE: A meta-narrative review has been conducted in 5 research databases (Web of Science, Science Direct, Scopus, Embase and Pubmed) without time limitations up to January of 2017 to address concerns related to the cost of and access to nivolumab and pembrolizumab in oncology health care. From each research base, articles were selected that had a key word related to the theme of pharmacoeconomics and nivolumab or pembrolizumab in any field of scientific work. The research questions were analyzed through the application of a meta-narrative review approach and the use of a convergence-coding matrix to summarize similarities and differences directly related to the research topic between the different papers. KEY FINDINGS: The first contribution of this meta-narrative review is that it summarizes economic-based works on the use of nivolumab and pembrolizumab, particularly for three therapeutic indications: melanoma, NSCLC and RCC. In general, despite the clinical benefit of nivolumab and pembrolizumab being well accepted and proven by scientific works, the published studies show that there are contradictory results with regard to the cost-effectiveness of these anti-PD-1s. The regulatory, economic and epidemiological variations mean that healthcare costs for cancer patients vary greatly from country to country and according to the type of tumor. The second contribution has to do with the recommendations for the development of high quality process for pharmacoeconomic analyses, especially in the new field of immuno-oncology. Finally, the third contribution is with regard to recommendations for the sustainable use of immunotherapies. CONCLUSIONS: Given the revolution in cancer therapy in recent years, the efficient allocation of existing resources is essential for healthcare systems to meet the evolving needs of populations and remain sustainable in the long term. The application of high quality information that stems from scientific evidence and economic modeling can help considerably to make the healthcare system sustainable over time mainly due to a higher number of therapeutic indications or more countries giving regulatory approval for the use of new and expensive cancer drugs.