Résumé
Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.
Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.
Sujets)
Tumeurs de l'ovaire , Coûts et analyse des coûts , Santé Complémentaire , Inhibiteurs de poly(ADP-ribose) polymérasesRésumé
Immuno-oncology studies the immune system in cancer. In recent decades, immunotherapy has shown a good response to the treatment of various locally advanced and metastatic cancers. The main mechanisms of action include stimulation of the patient's own immune system to enhance immune responses acting in tumor escape pathways. This review examined the literature related to immune system mechanisms in head and neck squamous cell carcinoma (HNSCC) and their application in immunotherapy using biomarkers. The PUBMED, LILACS, MEDLINE, WHOLIS, and SCIELO databases were searched using the terms squamous cell carcinoma, head and neck, immuno-oncology, immunotherapy, and immunology. The main drugs currently available for clinical use in patients diagnosed with HNSCC include pembrolizumab and nivolumab, both classified as check-point inhibitors. These immunobiological agents improve patient survival and quality of life. Many authors and clinical trials point out that the recommendation of these agents is linked to the dose of PD-L1 (ligand expressed primarily by tumor cells), which proved to be an unreliable biomarker in the patient selection. Recommendation of immunotherapy depends on reliable biomarkers that must be identified in order to achieve good therapeutic results.
Résumé
Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in innate immunity, immune regulation, maintenance of tissue homeostasis, and tissue repair and remodeling. Besides the conventional innate lymphocytes including NK cells and lymphoid tissue-inducer cells, the ILC family can be categorized into three groups, ILC1s, ILC2s and ILC3s. These non-cytotoxic ILC subsets have been identified to confer a diverse array of functions in oncogenesis and metastasis, immune surveillance, and antitumor immunity. In this review, we summarized the emerging findings in recent years regarding the roles of ILCs in immuno-oncology, and highlighted their potentials in immunotherapeutic approaches to tumors.
Résumé
Innate lymphoid cells ( ILCs) are a recently characterized family of immune cells that have critical roles in innate immunity, immune regulation, maintenance of tissue homeostasis, and tissue re-pair and remodeling. Besides the conventional innate lymphocytes including NK cells and lymphoid tissue-in-ducer cells, the ILC family can be categorized into three groups, ILC1s, ILC2s and ILC3s. These non-cyto-toxic ILC subsets have been identified to confer a diverse array of functions in oncogenesis and metastasis, immune surveillance, and antitumor immunity. In this review, we summarized the emerging findings in re-cent years regarding the roles of ILCs in immuno-oncology, and highlighted their potentials in immunothera-peutic approaches to tumors.
Résumé
Programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor has become one of the important treatment options for patients with advanced non-small cell lung cancer (NSCLC). However, only a small subset of patients with NSCLC can currently receive single-agent PD-1 inhibitors as first-line therapy, for the limitations of population selection exclude most patients from immuno-oncology (IO) monotherapy. In order to expand the candidate population for IO first-line treatment and make more newly diagnosed patients benefit from IO treatment, a series of studies are focusing on the combination of IO and other drugs in NSCLC. We reviewed the latest clinical data of IO first-line combination therapy in recent years, suggesting that on the basis of PD-1/PD-L1 inhibitors, combined with other IO, chemotherapy, anti-angiogenic drugs, targeted therapy or radiotherapy may produce synergistic anti-tumor effects. It is expected to benefit more newly diagnosed patients. .
Sujets)
Animaux , Humains , Carcinome pulmonaire non à petites cellules , Allergie et immunologie , Thérapeutique , Immunothérapie , Méthodes , Tumeurs du poumon , Allergie et immunologie , ThérapeutiqueRésumé
Objetivo: Realizar uma análise de custo-efetividade das terapias imuno-oncológicas anti-PD-1 aprovadas no Brasil versus ipilimumabe no tratamento do paciente sem tratamento prévio com melanoma metastático (estádios III ou IV), independentemente da mutação BRAF sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo com três estados de saúde mutuamente exclusivos (livre de progressão, progressão da doença e morte) para simular a condição clínica de pacientes tratados com nivolumabe ou pembrolizumabe comparado ao ipilimumabe. Os custos de medicamentos, materiais, exames e procedimentos foram calculados com base na lista oficial de preços no Brasil CMED (março/2017), revistas Kairos e Simpro, Planserv 2008 e CBHPM 2015. O desfecho clínico considerado para a análise foi de anos de vida salvos. Resultados: O nivolumabe produziu uma razão de custo-efetividade incremental de R$ 37.231 e o pembrolizumabe, de R$ 72.760. Ambas as intervenções demonstraram benefício clínico dentro do limiar de disposição a pagar recomendado pela OMS (três vezes o PIB per capita), mostrando que as tecnologias são custoefetivas. Na análise de sensibilidade univariada foi demonstrado que as RCEIs para ambas as análises foram mais sensíveis aos parâmetros referentes à taxa de desconto anual e aos custos de acompanhamento. Entre as terapias imuno-oncológicas anti-PD-1, o nivolumabe apresentou benefício clínico maior a um custo menor. Conclusão: Ambas as terapias anti-PD-1 (nivolumabe e pembrolizumabe) são custo-efetivas versus ipilimumabe, sugerindo-se o nivolumabe como melhor opção para a alocação de recursos no tratamento de pacientes sem tratamento prévio com melanoma avançado, independentemente da mutação BRAF, sob a perspectiva do sistema de saúde suplementar brasileiro.
Objective: The aim of this study was to evaluate the cost-effectiveness of anti-PD-1 therapies approved in Brazil versus ipilimumab for the treatment of previously untreated patients with metastatic melanoma (stage III/IV) irrespective of BRAF status under the Brazilian supplementary health system perspective. Methods: A cost-effectiveness model with three mutually exclusive health state (pre-progression, post-progression and death) was developed to simulate the clinical condition of patients with metastatic melanoma treated with nivolumab or pembrolizumab compared with ipilimumab. The cost of drugs, materials, exams and procedures were obtained from official Brazilian price list CMED, Kairos and Simpro magazines, Planserv 2008 and CBHPM 2015. The clinical outcome considered in the analysis was life years saved. Results: Nivolumab produced an incremental cost-effectiveness ratio of R$ 37,231 and pembrolizumab of R$ 72,760. Both interventions offered clinical benefit within the willingness-to-pay threshold recommended by World Health Organization (WHO) (three times per-capita GDP), showing that the technologies are cost-effective. It was demonstrated in the univariate sensitivity analyses that the parameters in which ICER of the comparison of nivolumab vs. ipilimumab and pembrolizumab vs. ipilimumab were more sensitive to annual discount rate (costs) and follow-up costs. Conclusion: Both nivolumab and pembrolizumab are cost-effective versus ipilimumab, suggesting that it would be more willing to be adopted for the treatment of previously untreated patients with advanced melanoma regardless of BRAF mutation under Brazilian supplementary health system perspective.
Sujets)
Humains , Analyse coût-bénéfice , Santé Complémentaire , MélanomeRésumé
Treatment of patients with advanced hepatocellular carcinoma (HCC) remains a huge challenge since a widely accepted therapeutic strategy has not been identified. There are some special features in patients with HCC in China, such as are mainly related to hepatitis B virus infection, often diagnosed as advanced or end-stage disease, and usually have a poorer prognosis compared with patients in western countries. Hence, appropriate treatments are urgently needed for these patients. Notably, immune-oncology therapy has been received increased attention in recent years. Based on promising results observed in clinical trials, immune-oncology therapy has been approved for treatment of various malignant diseases and brings a new hope to the treatment of advanced HCC. The review summarizes the current situation of advanced HCC treatment in China and discusses the prospects of immuno-oncology therapy.