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1.
Rev Prat ; 70(5): 471-474, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-33058629

RESUMO

Immune checkpoint inhibitors for treatment of advanced stage melanoma. Immunotherapy, which stimulates the anti-tumor immune response, has significantly modified the prognosis of advanced stage melanoma. Anti-CTLA4 monoclonal antibody, ipilimumab, showed a benefit on survival compared to chemotherapy in 2011. Anti-PD1, nivolumab and pembrolizumab subsequently showed superior clinical benefit including overall survival and tolerance over anti-CTLA4. Currently, the combination of ipilimumab and nivolumab appears as the most effective immunotherapy but the toxicity of this regimen is a limitation. Anti-PD1 antibodies have also been evaluated in the adjuvant setting for patients with stage III or IV resected melanoma where they have shown a significant benefit in term of relapse-free-survival. Studies are underway to evaluate these drugs in stage II resected melanoma and in neo-adjuvant setting with promising results.


Assuntos
Melanoma , Recidiva Local de Neoplasia , Humanos , Imunoterapia , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico
2.
Croat Med J ; 61(4): 326-332, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881430

RESUMO

AIM: To assess diseases outcomes and tolerability of real-life second-line nivolumab in a series of metastatic renal cell carcinoma (mRCC) patients. METHODS: This retrospective chart review involved prospectively monitored patients (named patient program) treated with second-line nivolumab for mRCC at the University Hospital Centre Zagreb from February 2016 to March 2018. RESULTS: The study enrolled 30 patients, 5 of whom (16.7%) had a complete response. The mean ± standard deviation therapeutic response time to nivolumab treatment was 14.07 ± 8.92 months, with a minimum treatment duration of 2 months and a maximum of 24 months. The median duration of therapy was 17 months (mean: 15.8 months; range: 3-24 months), and 50% (n=15/30) of patients remained alive at the end of follow up. The most common adverse events associated with nivolumab were fatigue (26.67%; n=8/30), anemia (10.0%; n=3/30), adrenal insufficiency (6.67%; n=2/30: G1=1, G2=1), grade 2 pneumonitis (6.67%; n=2/30), grade 2 neuropathy (6.67%; n=2/30), rash (6.67%; n = 2/30: G1=1, G2=1), and hepatitis (3.33%; n=1/30). CONCLUSION: The present study indicates acceptable patient responses and tolerability of nivolumab in mRCC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
3.
Anticancer Res ; 40(9): 5277-5283, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878817

RESUMO

BACKGROUND/AIM: The treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has remained challenging. The effect of salvage chemotherapy (SCT) after nivolumab has been identified recently in other cancer types. The aim of this study was to examine the efficacy of SCT after nivolumab treatment in patients with R/M HNSCC. PATIENTS AND METHODS: A retrospective study was conducted at four institutions in Japan. Fifty-six patients were enrolled in the study. RESULTS: The overall survival (OS) in SCT patients was significantly longer than that in best supportive care (BSC) patients. In the SCT patients, the median OS, median progression-free survival (PFS) and objective response rate (ORR) were 7.3 months, 2.3 months and 36%, respectively. Prognostic factor for OS and ORR was performance score (PS) and previous radiation, respectively. CONCLUSION: SCT after nivolumab is associated with better clinical outcomes in patients with R/M HNSCC compared to those receiving BSC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Recidiva , Retratamento , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(38): e22312, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957395

RESUMO

RATIONALE: Immunotherapy and targeted therapy have attracted widespread attention in current clinical research, which could be considered as a good therapeutic option for treatment of refractory liver cancer. PATIENT CONCERNS: The patient was a 37-year-old man with hepatitis B virus (HBV) infection. He was presented with hepatalgia and discomfort. DIAGNOSIS: The computed tomography showed multiple intrahepatic masses, indicating primary liver cancer with multiple intrahepatic metastases. INTERVENTIONS: After failed transarterial chemoembolization therapy, he was initially treated with immunotherapy pembrolizumab plus angiogenesis inhibitor lenvatinib, and after 3 months of treatment, the condition improved. However, the disease subsequently progressed. The next-generation sequencing identified a BRCA2 germline mutation in this patient. A poly (ADP-ribose) polymerase inhibitor, olaparib, plus nivolumab therapy was started and achieved stable disease. OUTCOMES: The patient achieved stable disease and improvement in hepatalgia for 3 months after the combination treatment of Olaparib and nivolumab. CONCLUSION: We identified a BRCA2 germline mutation in a patient with liver cancer. Our findings could offer an alternative management for patients with liver cancer harboring germline BRCA2 mutation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/uso terapêutico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Evolução Fatal , Genes BRCA2 , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Masculino
5.
Lancet Haematol ; 7(9): e660-e670, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853585

RESUMO

BACKGROUND: Recognising that the immune suppressive microenvironment promotes tumour growth in Hodgkin lymphoma, we hypothesised that activating immunity might augment the activity of targeted chemotherapy. We evaluated the safety and activity of combinations of brentuximab vedotin with nivolumab or ipilimumab, or both in patients with relapsed or refractory Hodgkin lymphoma. METHODS: In this multicentre, open-label, phase 1/2 trial, patients with relapsed or refractory Hodgkin lymphoma aged 18 years or older who had relapsed after at least one line of therapy, with an Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ and marrow function, with no pulmonary dysfunction were eligible for inclusion. Phase 1 primary objectives were to determine the maximum tolerated dose and dose limiting toxicities of brentuximab vedotin combined with ipilimumab (ipilimumab group), nivolumab (nivolumab group), or both (triplet therapy group) using a 3 + 3 dose escalation design with expansion cohorts. During the dose escalation phase, patients were enrolled sequentially into one of six cohorts: in the ipilimumab group fixed brentuximab vedotin 1·8 mg/kg with ipilimumab 1 mg/kg (cohort A) or 3 mg/kg (cohort B); in the nivolumab group fixed nivolumab 3 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort D) or 1·8 mg/kg (cohort E); and in the triplet therapy group fixed nivolumab 3 mg/kg and ipilimumab 1 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort G) or 1·8 mg/kg (cohort H). Additional patients were enrolled in the expansion phase at the same doses of cohorts B, E, and H. All drugs were given intravenously; brentuximab vedotin and nivolumab were given every 3 weeks, ipilimumab was given every 6 weeks in the ipilimumab group and every 12 weeks in the triplet therapy group. All eligible and treated patients were included in the analysis. This phase 1/2 study is registered with ClinicalTrials.gov, NCT01896999. The phase 2, randomised portion of the trial is still enrolling. FINDINGS: Between March 7, 2014, and Dec 28, 2017, 64 patients were enrolled; two patients in the ipilimumab group and one patient in the nivolumab group were excluded due to ineligibility after enrolment and 61 were evaluable. A total of six dose limiting toxicities were reported in four patients, and the doses used in cohorts B, E, and H were established as maximum tolerated doses and patients were subsequently enrolled onto expansion cohorts (C, F, and I) with these schedules. There were ten (43%) grade 3-4 treatment related adverse events in the ipilimumab group, three (16%) in the nivolumab group, and 11 (50%) in the triplet therapy group including: eight (13%) of 64 patients reporting rash, and colitis, gastritis, pancreatitis and arthritis, and diabetic ketoacidosis each occurring in one (2%) patient. There were two (3%) treatment related deaths, one in the nivolumab group and one in the triplet therapy group. The overall response rate was 76% (95% CI 53-92) in the ipilimumab group, 89% (65-99) in the nivolumab group, and 82% (60-95) in the triplet therapy group, and the complete response rate was 57% (95% CI 34-78%) in the ipilimumab group, 61% (36-83%) in the nivolumab group, and 73% (50-89%) in the triplet therapy group. With a median follow-up of 2·6 years (IQR 1·8-2·9) in the ipilimumab group, 2·4 years (2·2-2·6) in the nivolumab group, and 1·7 years (1·6-1·9) in the triplet therapy group, median progression-free survival is 1·2 years (95% CI 1·7-not reached) in the ipilimumab group, but was not reached in the other two treatment groups. Median overall survival has not been reached in any of the groups. INTERPRETATION: There are clear differences in activity and toxicity of the three combination regimens. The tolerability and preliminary activity for the two most active regimens, brentuximab vedotin with nivolumab and the triplet therapy, are being compared in a randomised phase 2 trial (NCT01896999). FUNDING: Eastern Cooperative Oncology Group-American College of Radiology Imaging Network and the National Cancer Institute of the National Institutes of Health.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Hipersensibilidade/etiologia , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Dor/etiologia , Intervalo Livre de Progressão , Recidiva , Taxa de Sobrevida , Resultado do Tratamento
7.
Brasília; S.N; 23 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117682

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos e 8 protocolos.


Assuntos
Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Esteroides/uso terapêutico , Avaliação da Tecnologia Biomédica , Vacina BCG/uso terapêutico , Heparina/uso terapêutico , Almitrina/uso terapêutico , Estudos de Coortes , Corticosteroides/uso terapêutico , Enoxaparina/uso terapêutico , Azitromicina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Darunavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ipilimumab/uso terapêutico , Fondaparinux/uso terapêutico , Nivolumabe/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
8.
Anticancer Res ; 40(8): 4229-4236, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727749

RESUMO

AIM: Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. PATIENTS AND METHODS: Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. RESULTS: The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. CONCLUSION: The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Análise de Sobrevida , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Nivolumabe/genética , Análise de Regressão , Estudos Retrospectivos
9.
Bull Cancer ; 107(9): 946-958, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32646604

RESUMO

It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P=0.01) and a better OS (HR=2, P=0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR=0.4, 95% CI [0.19; 0.8], P=0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having≥2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Nivolumabe/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida
10.
Bull Cancer ; 107(5S): S49-S55, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620207

RESUMO

Local and systemic immunotherapies are used for the management of bladder cancer in daily practice. BCG has been administered for almost 40 years in patients with non-muscle invasive bladder cancer (NMIBC). Despite its efficacy, disease progression is observed in nearly 30% of patients. Given the antitumor activity of immune checkpoint inhibitors in metastatic setting, these therapies are currently investigated in NMIBC. Pembrolizumab is now approved by the Food and Drug Administration (FDA) for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have not elected to undergo cystectomy. Several phase 3 trials are ongoing to investigate the efficacy of PD(L)1 inhibitors combined with BCG such as ALBAN study in France.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Humanos , Invasividade Neoplásica , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/patologia
11.
Medicine (Baltimore) ; 99(21): e20464, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481351

RESUMO

INTRODUCTION: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. PATIENT CONCERNS: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. DIAGNOSIS: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. INTERVENTIONS: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. OUTCOMES: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. LESSONS: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy.


Assuntos
Glomerulonefrite por IGA/etiologia , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Glomerulonefrite por IGA/fisiopatologia , Humanos , Japão , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Nivolumabe/uso terapêutico , Veia Porta/anormalidades , Veia Porta/fisiopatologia , Trombose
12.
Eur Urol Focus ; 6(5): 1086-1096, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540268

RESUMO

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response.


Assuntos
Betacoronavirus/metabolismo , Carcinoma de Células Renais/metabolismo , Infecções por Coronavirus/metabolismo , Neoplasias Renais/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Insuficiência Renal Crônica/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Carcinoma de Células Renais/epidemiologia , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hospitalização , Humanos , Ipilimumab/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/epidemiologia , Biópsia Líquida , Nivolumabe/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Inibidores de Proteínas Quinases/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Serina Endopeptidases/metabolismo , Índice de Gravidade de Doença , Sunitinibe/uso terapêutico
13.
J Cancer Res Clin Oncol ; 146(10): 2699-2707, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32474752

RESUMO

BACKGROUND: Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. METHODS: We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS). RESULTS: Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a < 10% chance of yielding a benefit from CKI. CONCLUSIONS: Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Peritoneais/secundário , Neoplasias Pleurais/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/imunologia , Neoplasias Pleurais/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Estudos Retrospectivos
14.
J Cancer Res Clin Oncol ; 146(11): 3025-3036, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32583235

RESUMO

PURPOSE: Although immune checkpoint inhibitors have been shown to be effective in many clinical trials, real-world data remain limited. We investigated the outcomes of non-small cell lung cancer (NSCLC) patients who received nivolumab, with an emphasis on hyper-progressive disease (HPD). METHODS: This retrospective study enrolled stage IV NSCLC patients who received nivolumab after progression on prior chemotherapy between July 2016 and June 2018 at a single center in Korea. HPD was defined by response evaluation criteria in solid tumors as progression at the first evaluation, with a ≥ two-fold increase in the tumor growth rate during nivolumab treatment. RESULTS: A total of 83 patients with a median age of 60 years were enrolled [squamous, 25(30%) and non-squamous, 58(70%)]. The median progression-free survival (PFS) and overall survival (OS) were 2.6 months [95% confidence interval (CI) 0.82-4.31] and 8.6 months (95% CI 5.56-11.59), respectively. HPD developed in 16 (19.2%). The median OS of HPD patients was 2.2 months (95% CI 0.92-3.75) compared with 4.1 months for progressive disease (PD) patients without HPD (95% CI 1.54-6.67). Among patients with pleura or pericardium metastasis, increased effusion was seen more frequently in HPD patients compared with PD patients without HPD [90% (9/10) vs. 28.6% (4/14); p = 0.005]. HPD patients also showed a significant decrease in circulating albumin after treatment with nivolumab (p = 0.030). CONCLUSION: Although the efficacy of nivolumab in real-world patients was comparable to that seen in clinical trials, clinicians should be aware of HPD because it is not uncommon and represents a worse prognosis.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
15.
Int J Clin Oncol ; 25(8): 1533-1542, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32519026

RESUMO

BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
16.
J Comput Assist Tomogr ; 44(4): 619-626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558769

RESUMO

OBJECTIVE: The aim of the study was to study clinical, imaging findings, response patterns, and immune-related adverse events in classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) patients treated with immune checkpoint inhibitors (ICIs). METHODS: A retrospective search was performed to identify patients with relapsed/refractory cHL and NHL treated with ICIs from 2015 to 2019. Clinical and laboratory data were collected. Imaging studies were reviewed for treatment response and immune-related adverse events. RESULTS: Ten patients with relapsed/refractory cHL (median age, 41 years) and 14 patients with relapsed/refractory NHL (median age, 61 years) were identified. Overall response rate was 70% for cHL patients. None of the NHL patients demonstrated complete or partial response. One case of hyperprogression and one case with atypical response were radiologically detected in cHL patients. Hypothyroidism requiring treatment occurred in 2 (20%) of 10 cHL patients, one of which had imaging correlate. Of 14 NHL patients, 1 (7%) had radiologic evidence of pneumonitis and 1 (7%) had colitis. CONCLUSIONS: This single-institution observational study demonstrated that overall response rate was higher in patients with cHL undergoing ICI. Immune checkpoint inhibitor therapy has unique response patterns and toxicities in both cHL and NHL patients that radiologists should keep in mind.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Colite/epidemiologia , Doença de Hodgkin/tratamento farmacológico , Hipotireoidismo/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Pneumonia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Feminino , Doença de Hodgkin/diagnóstico por imagem , Humanos , Hipotireoidismo/induzido quimicamente , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Pneumonia/induzido quimicamente , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
17.
Gan To Kagaku Ryoho ; 47(6): 923-926, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541169

RESUMO

BACKGROUND: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients. METHODS: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined. RESULTS: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group. CONCLUSION: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.


Assuntos
Linfócitos , Neutrófilos , Nivolumabe/uso terapêutico , Neoplasias Gástricas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
18.
Lima; Instituto Nacional de Salud; jun. 2020.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1122695

RESUMO

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Instituto Nacional de Enfermedades Neoplásicas; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: Adultos con melanoma irresecable o metastásico; I: Nivolumab; C: Quimioterapia o nivolumab + ipilimumab; O: sobrevida global, libre de progresión, tasa de respuesta y eventos adversos. A. Cuadro clínico El melanoma es un tumor producido por la trasformación maligna de los melanocitos. El melanoma es el tercer tipo más común de cáncer de piel, aunque constituye el tipo más agresivo y responsable del mayor número de muertes. A nivel mundial, se estima una tasa de incidencia anual estandarizada según edad de 3,1 por cada 100 000 y una tasa de mortalidad anual estandarizada según edad de 0,63 por cada 100 000. En Perú, se estima anualmente 944 casos nuevos de melanoma cutáneo y 355 muertes. En la última década, avances en inmunoterapia y terapia dirigida han mejorado notablemente los resultados para pacientes con melanoma avanzado. B. Tecnología sanitaria Nivolumab es un anticuerpo monoclonal humano que se une al receptor de muerte programada 1 (PD1) en las células T y bloquea su unión con los ligandos PD-L1 y PD-L2, liberando la inhibición de la respuesta inmune antitumoral. Se indica como tratamiento para el melanoma irresecable o metastásico como agente simple o en combinación ipilimumab. La dosis recomendada es 240 mg cada 2 semanas o 480 mg cada 4 semanas. Las reacciones adversas son de carácter leve, aunque se ha observado eventos adversos graves relacionados con el sistema inmunitario, como neumonitis, colitis, hepatitis, endocrinopatías, nefritis, disfunción renal y encefalitis. Nivolumab cuenta con aprobación de la Food and Drug Administration (FDA) desde el año 2014 y en Perú cuenta con un registro sanitario vigente. OBJETIVO; Describir la evidencia científica disponible sobre la eficacia y seguridad de nivolumab para el tratamiento de pacientes con melanoma irresecable o metastásico. METODOLOGÍA; Se realizó una búsqueda sistemática en Medline (Pubmed), The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados, revisiones sistemáticas (RS) con o sin meta-análisis (MA) de ensayos clínicos aleatorizados controlados, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando AMSTAR 2 para RS y la herramienta propuesta por la colaboración Cochrane para ensayos clínicos, AGREE II para valorar el rigor metodológico de las GPC y GRADE para evaluar la calidad de los desenlaces. RESULTADOS: Se identificó dos revisiones sistemáticas, cuatro guías de práctica clínica y cuatro evaluaciones de tecnología sanitaria que respondieron a la pregunta PICO de interés. CONCLUSIONES: Comparado con dacarbazina o quimioterapia, nivolumab mejoró significativamente la sobrevida global, sobrevida libre de progresión y la probabilidad de alcanzar respuesta parcial o completa. Nivolumab mostró similar eficacia respecto a nivolumab + ipilimumab. La evaluación de seguridad mostró similar riesgo de eventos adversos entre la monoterapia con nivolumab, terapia combinada con nivolumab + ipilimumab y quimioterapia o dacarbazina. Solo se observó un incremento en el riesgo prurito o rash cutáneo asociado al consumo de nivolumab en monoterapia, comparado con quimioterapia o dacarbazina. Las GPC de ESMO, NCCN, SIGN y NICE recomiendan nivolumab en monoterapia o terapia combinada con ipilimumab como alternativa de tratamiento del melanoma irresecable o metastásico. La ETS incluidas mostraron decisiones variables respecto a la cobertura de nivolumab en melanoma irresecable o metastásico. DIGEMID no recomienda su cobertura obligatoria debido a su elevado costo. IETSI e IECS recomiendan dar cobertura, aunque manifiestan que el costo limitaría potencialmente su uso, y recomiendan evaluar el costo-efectividad de la tecnología durante el periodo de aprobación de uso. NICE recomienda la cobertura con nivolumab como alternativa de tratamiento para el melanoma irresecable o metastásico. La evidencia procede de meta-análisis en red de comparaciones mixtas. Las revisiones sistemáticas fueron consideradas como nivel de confianza bajo. La calidad de la evidencia de los desenlaces evaluados fue baja o moderada. Las GPC incluidas obtuvieron un puntaje entre 61,5% y 78% en la valoración global de calidad.


Assuntos
Humanos , Nivolumabe/uso terapêutico , Melanoma/tratamento farmacológico , Metástase Neoplásica , Peru , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício
19.
Lung Cancer ; 145: 213-215, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-165217
20.
Gan To Kagaku Ryoho ; 47(4): 725-727, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389997

RESUMO

BACKGROUND: Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1(PD-1), was approved for use in the treatment of patients with advanced gastric or gastroesophageal junction cancer who had been previously treated with B2 chemotherapy regimens in Japan. METHODS: We investigated the efficacy of nivolumab therapy in 15 consecutive patients with advanced gastric cancer between October 2017 and December 2018 in our facility. RESULTS: In our study, the 6-month overall survival rate was 67.7%, and the median survival time(MST)was 6.3 months. Immune-related adverse events(irAEs)occurred in the following patients: 2 patients, interstitial pneumonia(13%); 1 patient, myocarditis (6.7%); 1 patient, hypothyroidism(6.7%); and 1 patient, liver dysfunction(6.7%). Of the patients with an absolute lym- phocyte count(ALC)of C2,000/mL at baseline, 33%(4/12)experienced irAEs, while of those with an ALC of >2,000/mL, 67% had irAEs. The 6-month overall survival rate was better in patients with an ALC >1,600/mL(100%, 4/4)than in those with an ALC of C1,600/mL(35%, 4/11). The 6-month overall survival rate of the patients with a neutrophil-to-lymphocyte ratio(NLR)of <4 was 63%, which was better than the 33% rate in those with an NLR of B4. CONCLUSIONS: Nivolumab therapy was a safe and feasible treatment option. The cutoff values of ALC of 2,000/mL for irAEs and of ALC of 1,600/mL and NLR of 4 for prognosis might be effective surrogate markers in nivolumab treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Gástricas , Humanos , Japão , Neoplasias Pulmonares , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
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