Diagnostic Accuracy of Next Generation Sequencing Panel using Circulating Tumor DNA in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Until now, no meta-analysis has been published to evaluate the diagnostic performance of next-generation sequencing (NGS) panel using circulating tumor (ctDNA) in patients with advanced non-small cell lung cancer (aNSCLC). The aim of the study was to carry out a systematic review and a meta-analysis in order to determine the accuracy of NGS of ctDNA to detect six oncogenic driver alterations: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1); serine/threonine-protein kinase B-RAF (BRAF); RET proto-oncogene (RET); and MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 in patients with aNSCLC. METHODS: MEDLINE/PubMed, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and Centre for Reviews and Dissemination databases and articles obtained from other sources were searched for relevant studies that evaluate the accuracy (sensitivity and specificity) of NGS using ctDNA in patients with aNSCLC. The studies were eligible when NGS of ctDNA was compared with tissue tests to detect at least one of the six oncogenic driver alterations. Diagnostic measures (sensitivity and specificity) were pooled with a bivariate diagnostic random effect. All statistical analyses were performed with software R, v.4.0.0. RESULTS: Ten studies were eligible for data extraction. The overall pooled estimates of sensitivity and specificity were 0.766 (95% CI: 0.678-0.835); 0.999 (95% CI: 0.990-1.000), respectively. CONCLUSIONS: The analysis has demonstrated that the NGS panel using ctDNA has a high accuracy to identify the six actionable oncogenic driver alterations in patients with aNSCLC. Therefore, it can be considered a reliable alternative to guide the patients with aNSCLC to the right treatment who cannot undergo an invasive procedure or have insufficient tissue material for molecular tests.

Cost-effectiveness analysis of the SP142 versus 22C3 PD-L1 assays in the treatment of atezolizumab plus nab-paclitaxel for patients with advanced triple negative breast cancer in the Brazilian private healthcare system.

OBJECTIVE: The aim of the study was to demonstrate the clinical and economic impact of two PD-L1 IHC assays, SP142 versus 22C3, to identify the eligibility of the patients with advanced triple negative breast cancer (aTNBC) to the treatment with atezolizumab plus nab-paclitaxel in the Brazilian private healthcare system (BPHS). METHODS: The study performed a cost-effectiveness analysis based on a partitioned-survival model with three mutually exclusive health states: progression-free (PF), progression, and death. Data of progression-free survival and overall survival were extracted from a retrospective exploratory analysis of IMpassion130, an analytical harmonization of PD-L1 IHC assays. The analyses included only direct costs (drug acquisition and management of adverse events) that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED PF18% (Câmara de Regulação do Mercado de Medicamentos) tables. A probabilistic sensitivity analysis was performed as a second-order Monte Carlo Simulation in order to evaluate the uncertainties of the model. RESULTS: The SP142 assay has the potential to improve PFS and generate savings to the BPHS. The incremental cost-effectiveness ratio (ICER) was -USD 4,119.43 per month of progression-free survival. CONCLUSIONS: The SP142 assay demonstrated to be a dominant alternative compared to 22C3 to guide the treatment with atezolizumab plus nab-paclitaxel in patients with aTNBC.

Economic evaluation of the SP142 versus 22C3 PD-L1 assays in the treatment of atezolizumab plus nab-paclitaxel for patients with advanced triple negative breast cancer in the Brazilian private healthcare systemp / Avaliação econômica dos testes de PD-L1 SP142 versus 22C3 no tratamento com atezolizumabe mais nab-paclitaxel em pacientes com câncer de mama triplo-negativo avançado no sistema de saúde suplementar no Brasil

Objective: The aim of the study was to demonstrate the economic impact of two PD-L1 immunohistochemistry (IHC) assays, SP142 versus 22C3, in the treatment with atezolizumab plus nab-paclitaxel in patients with advanced triple negative breast cancer (aTNBC) in the Brazilian private healthcare system (BPHS). Methods: The study performed two analyses: one per patient and other of the potential population projected for the BPHS (budget impact analysis). Data of progressionfree survival and overall survival were extracted from a post hoc analysis of the IMpassion130 trial to develop a partitioned-survival model to simulate the economic impact of the treatment with atezolizumab plus nab-paclitaxel guided by the SP142 and 22C3 assays on patients with aTNBC. The analyses included only direct costs that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED (Câmara de Regulação do Mercado de Medicamentos) PF18% tables. A univariate sensitivity analysis was performed with the parameters varying ± 20%. Results: The study has demonstrated that the SP142 assay has the potential to save ­BRL 179,730 with the treatment of atezolizumab plus nab-paclitaxel per patient with aTNBC in five years. Conclusion: The SP142 assay can optimize the use of atezolizumab plus nab-paclitaxel avoiding its prescription in patients who will not have a significant clinical improvement.

Objetivo: O objetivo do estudo foi demonstrar o impacto econômico de dois testes de imuno-histoquímica, SP142 versus 22C3, no tratamento com atezolizumabe + nab-paclitaxel em pacientes com câncer de mama triplo-negativo avançado (CMTNa) no sistema de saúde suplementar (SSS) no Brasil. Métodos: O estudo realizou duas análises: uma por paciente e outra na população potencial projetada para o SSS (análise de impacto no orçamento). Dados de sobrevida livre de progressão e de sobrevida global foram extraídos da análise post hoc do estudo IMpassion130 para o desenvolvimento de um modelo de sobrevida particionado que simulasse o impacto econômico do tratamento com atezolizumabe + nab-paclitaxel direcionado pelos testes SP142 e 22C3 em pacientes com CMTNa. A análise considerou somente os custos diretos baseados nas tabelas CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) e CMED (Câmara de Regulação do Mercado de Medicamentos) PF18%. Uma análise de sensibilidade univariada foi realizada variando os parâmetros em ± 20%. Resultados: O estudo demonstrou que o teste SP142 apresenta um potencial de economia de -179.730 reais (BRL) no tratamento de atezolizumabe + nab-paclitaxel por paciente com CMTNa em cinco anos. Conclusão: O uso do teste SP142 possibilita otimizar o uso de atezolizumabe + nab-paclitaxel evitando a sua prescrição em pacientes que não irão se beneficiar de forma significativa.

Análise de custo-efetividade do painel de sequenciamento de nova geração do DNA circulante tumoral no diagnóstico dos pacientes com câncer de pulmão de não pequenas células não escamoso metastático / Cost-effectiveness analysis of next generation sequencing panel of circulating tumor DNA in the diagnosis of patient with metastatic non-squamous non- small cell lung cancer

Objetivo: Avaliar o impacto clínico e econômico do uso do perfil genômico utilizando Next Generation Sequencing (NGS) em DNA circulante tumoral (ctDNA) na escolha do tratamento de primeira linha (1L) dos pacientes com câncer de pulmão de células não pequenas, não escamoso, metastático e que não apresentam material tecidual suficiente para avaliação das mutações oncogênicas. Métodos: Foi realizada uma análise de custo-efetividade com base em um modelo de árvore de decisão e um modelo de Markov para simular os resultados dos testes diagnósticos e consequentemente o seu impacto clínico e econômico na primeira linha de tratamento. O comparador da análise foi o teste de mutações específicas no gene EGFR por ctDNA. As terapias medicamentosas incluídas na análise foram as terapias-alvo de EGFR e ALK, que estão incorporadas no rol da Agência Nacional de Saúde Suplementar, e a imunoterapia pembrolizumabe combinada à quimioterapia. Os desfechos clínicos foram retirados dos estudos clínicos das terapias avaliadas no modelo. Resultados: O uso do painel de NGS em ctDNA demonstrou uma economia de -R$ 2.076,35 por paciente em um ano, e os resultados de RCEI foram: -R$ 7.652,56 (R$/SLP) e -R$ 33.742,14 (R$/SG). Conclusão: O painel de NGS em ctDNA demonstrou ser uma alternativa dominante em relação ao teste de EGFR em ctDNA.

Objective: The aim of this study was to evaluate the clinical and economic impact of the next generation sequencing (NGS) panel of circulating tumor DNA (ctDNA) in the clinical decision of first line treatment for patients with metastatic non-squamous non-small cell lung cancer who lack of tissue material for evaluation of oncogenic driver mutations. Methods: A cost-effectiveness analysis was performed based on a decision tree model and a Markov model in order to simulate the results of diagnostic tests and therefore its clinical and economic impact in the first line of treatment. The comparators were the single EGFR mutation detection methodologies in ctDNA. The analysis included the anti-EGFR and anti-ALK target therapies; and the combined therapy of pembrolizumab plus chemotherapy. Clinical outcomes were derived from clinical trials of the therapies included in the model. Results: The use of the NGS ctDNA panel showed a saving of -R$ 2,076.35 and the results of the ICER were -R$ 7,652.56 (R$/SLP) and -R$ 33,742.14 (R$/SG). Conclusion: The NGS panel demonstrated to be a dominant alternative in comparison to ctDNA EGFR testing.

Análise de impacto orçamentário do uso da razão dos testes sFlt-1: PlGF na exclusão de pré-eclâmpsia em mulheres com suspeita clínica na perspectiva do sistema de saúde suplementar / Budget impact analysis of sFlt-1/PlGF ratio to help rule-out pre-eclampsia in women presenting with clinical suspected in the private healthcare system perspective in Brazil

Objetivo: O objetivo do estudo foi avaliar o impacto econômico da incorporação da razão dos testes tirosina quinase-1 solúvel (sFlt-1):fator de crescimento placentário (PlGF) no auxílio da exclusão da pré-eclâmpsia na perspectiva do Sistema de Saúde Suplementar do Brasil (SSS). Métodos: Foi desenvolvido um modelo de decisão com o intuito de simular as decisões clínicas do manejo das pacientes com suspeita de pré-eclâmpsia entre a 24ª semana e a 36ª semana + 6 dias de gestação utilizando a razão dos testes sFlt-1:PlGF em comparação com cenário sem o teste. Os dados clínicos utilizados no modelo foram derivados do estudo PROGNOSIS. A análise incluiu apenas custos diretos que foram baseados na Tabela CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) e na Tabela CMED PF 18% (Câmara de Regulação do Mercado de Medicamentos). Uma análise de sensibilidade univariada foi conduzida com variação de 15% dos parâmetros. Resultados: A razão dos testes sFlt-1:PlGF apresentou um potencial de economia de -R$ 4.532,04 por paciente comparado ao cenário sem teste. Considerando a incorporação no SSS, a razão dos testes sFlt-1:PlGF pode promover uma economia de -R$ 6.375.865,68 em 2021 e um acumulado de -R$ 136.495.533,87 em cinco anos. Conclusão: O uso da razão sFlt-1:PlGF no auxílio da exclusão da pré-eclâmpsia tem potencial de melhorar as decisões clínicas e, consequentemente, evitar hospitalizações desnecessárias. A incorporação do teste pode promover uma economia substancial para o sistema de saúde suplementar

Objective: The aim of this study was to evaluate the economic impact of the incorporation of the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test in the private healthcare system in Brazil (SSS). Methods: A decision model was developed in order to simulate the clinical decisions of the management of women with suspected pre-eclampsia between 24 weeks and 36 weeks plus 6 days with sFlt-1:PlGF ratio test, compared with no test scenario. The clinical data used in the model were derived from PROGNOSIS study. The analysis included only direct costs that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED PF 18% (Câmara de Regulação do Mercado de Medicamentos). A univariate sensitivity analysis was conducted with a variation of 15%. Results: The sFlt-1:PlGF ratio test has the potential to save -R$ 4.532,04 per patient compared to no test scenario. Considering the incorporation of the test in SSS, the sFlt1:PlGF ratio test can promote an economy of -R$ 6.375.865,68 in 2021 and -R$ 136.495.533,87 in accumulated five years of. Conclusion: The use of sFlt-1:PlGF ratio test to help rule-out pre-eclampsia has the potential to improve clinical decision and therefore to reduce unnecessary hospitalizations. The incorporation of the test can promote a substantial saving to the private healthcare system.