Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 104
Filtrar
1.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704852

RESUMO

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Tuberculose Latente/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo
2.
Anticancer Res ; 39(11): 6265-6271, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704856

RESUMO

BACKGROUND/AIM: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. RESULTS: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. CONCLUSION: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.


Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Japão , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
3.
Rinsho Ketsueki ; 60(9): 1341-1350, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597862

RESUMO

It has been eight years since the first immune checkpoint-blocking antibody, ipilimumab, was approved for metastatic malignant melanoma treatment by FDA in 2011. During this period, several other immune checkpoint blockers have been newly developed and approved for certain cancers, including malignant melanoma. However, there have been several concerns with some of these. The overall response rate did not exceed 30% in many cancers; although combination therapy with ipilimumab and nivolumab increased efficacy, immune-related adverse events also increased. This observation facilitated the reverse translational research (rTR) approach, using clinical specimens from treated patients to gradually elucidate the mechanism of resistance and biomarkers to select patients who can potentially benefit from immunotherapy. This has also promoted the development of novel combination therapies. In this review, immunological findings that highlight the resistance mechanisms of cancers against immune checkpoint blockers and the novel attempts to achieve a break-through will be discussed.


Assuntos
Imunoterapia , Ipilimumab/uso terapêutico , Melanoma/terapia , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/terapia , Resistencia a Medicamentos Antineoplásicos , Humanos , Pesquisa Médica Translacional
4.
Medicine (Baltimore) ; 98(40): e17164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577707

RESUMO

INTRODUCTION: The PD-1 inhibitors have shown good response in the treatment for many types of malignant tumors, but as monotherapy for advanced esophageal squamous carcinoma, the objective response rate is low. Here we report a case of the patient with advanced esophageal squamous cell carcinoma (ESCC) showing a completely response to nivolumab combined with a small molecule multi-target tyrosine kinase inhibitor (TKI) anlotinib. PATIENT CONCERNS: A 61-year-old male was put under a surgery as the response to the diagnosis of ESCC in March 2014. The post-operative follow-up in March 2018 suggested a recurrence based on imagological findings, and symptoms such as shortness of breath and cough were also observed in October 2018. DIAGNOSIS: The patient was diagnosed as advanced metastatic ESCC in October 2018. INTERVENTIONS: Radical resection and esophagogastrostomy under aortic arch with left thoracotomy was performed in March 2014. As a treatment against the post-surgical recurrence, 4 courses of paclitaxel combined with nedaplatin was administered in April 2018 with an outcome of PR, followed by a combined administration of Nivolumab and anlotinib in November 2018. OUTCOMES: Chest CT during a 3-month follow-up revealed the disappearance of all the metastases, and no adverse effect was observed during the treatment. CONCLUSION: The combined treatment of nivolumab and anlotinib is likely to be considered as an optional management of advanced ESCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Indóis/uso terapêutico , Nivolumabe/uso terapêutico , Quinolinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
5.
Gan To Kagaku Ryoho ; 46(10): 1513-1523, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631132

RESUMO

Nivolumab, anti-PD-1 monoclonal antibody, has innovated treatment ofpatients with gastric cancer. Nivolmab has been indicated forBthird-line treatment ofgastric cancer patients in September 2017. Although it has been more than 1 year after nivolumab being widely used in practice, we still have many clinical questions in this population. We leverage evidence obtained from other types of cancer where we have more experience to use nivolumab to answer these questions step by step, but it is still far from enough with some complexities unique to gastric cancer. While nivolumab monotherapy has shown long term survival in some patients, more than halfofpatients experience disease progression right after treatment initiation with nivolumab. Because we have other treatment options, it is urgent to identify biomarkers to predict its efficacy. Now clinical trials ofimmune -checkpoint inhibitors in various treatment line are ongoing with translational research including biomarker analysis and we highly expect those outcome.


Assuntos
Nivolumabe/uso terapêutico , Neoplasias Gástricas , Anticorpos Monoclonais , Humanos , Neoplasias Gástricas/tratamento farmacológico
6.
Gan To Kagaku Ryoho ; 46(10): 1614-1616, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631152

RESUMO

Immunocheckpoint inhibitors including anti-PD-1 antibody have shown certain therapeutic effects on various cancer types. They have also attracted great attention as novel cancer treatment options in addition to surgical resection, chemotherapy, and radiation therapy. Herein, we report a case of gastric cancer that was successfully treated with conversion surgery after nivolumab treatment. The patient was 68 years old and male. Upper gastrointestinal endoscopy revealed a type 3 tumor in the antrum, and he was referred to our department for further examination. The gastric cancer was diagnosed as cT4aN2M0, cStage ⅢA, and he was administered SOX as the first-line and nab-PTX/RAM as the second-line treatment, which was also a PD. As the third-line treatment, nivolumab showed remarkable reduction of the tumor after initiation, and after 14 courses, conversion surgery was performed. The patient remains alive without recurrence.


Assuntos
Nivolumabe/uso terapêutico , Neoplasias Gástricas , Idoso , Humanos , Masculino , Recidiva Local de Neoplasia
7.
Cancer Immunol Immunother ; 68(9): 1493-1500, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31501955

RESUMO

Immunotherapy with checkpoint inhibitors revolutionized melanoma treatment in both the adjuvant and metastatic setting, yet not all metastatic patients respond, and metastatic disease still often recurs among immunotherapy-treated patients with locally advanced disease. TNFSF4 is a co-stimulatory checkpoint protein expressed by several types of immune and non-immune cells, and was shown in the past to enhance the anti-neoplastic activity of T cells. Here, we assessed its expression in melanoma and its association with outcome in locally advanced and metastatic disease. We used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE), and RNA sequencing data from anti-PD1-treated patients at Sheba medical center. TNFSF4 mRNA is expressed in melanoma cell lines and melanoma samples, including those with low lymphocytic infiltrates, and is not associated with the ulceration status of the primary tumor. Low expression of TNFSF4 mRNA is associated with worse prognosis in all melanoma patients and in the cohorts of stage III and stage IIIc-IV patients. Low expression of TNFSF4 mRNAs is also associated with worse prognosis in the subgroup of patients with low lymphocytic infiltrates, suggesting that tumoral TNFSF4 is associated with outcome. TNFSF4 expression was not correlated with the expression of other known checkpoint mRNAs. Last, metastatic patients with TNFSF4 mRNA expression within the lowest quartile have significantly worse outcome on anti-PD1 treatment, and a significantly lower response rate to these agents. Our current work points to TNFSF4 expression in melanoma as a potential determinant of prognosis, and warrants further translational and clinical research.


Assuntos
Imunoterapia/métodos , Melanoma/metabolismo , Ligante OX40/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Ligante OX40/genética , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Análise de Sobrevida , Resultado do Tratamento
8.
DNA Cell Biol ; 38(10): 1143-1146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464522

RESUMO

Cervical carcinoma is associated with high-risk human papillomavirus (HPV) DNA integration and usually occurs after age 21 (peak 45 years), as reflected in screening guidelines. Between 1999 and 2008, cervical carcinoma rate in adolescents aged 15-19 years was 0.15 per 100,000. HPV-negative cervical carcinoma is rare in adolescents. The youngest previously reported case was 15 years old. Treatment options for cervical carcinoma are limited after first-line therapy. Immune checkpoint inhibitors blocking programmed death receptor (PD-1) and its ligand, PD-L1, have shown objective clinical responses and are tolerable in adults with gynecologic cancers. This class of agents is well tolerated in pediatric patients. PD-1/PD-L1 is commonly expressed in gynecologic cancers but its expression may not predict clinical response. We describe an exceptional response to single agent nivolumab postradiation therapy in a 13-year-old adolescent with poorly differentiated cervical carcinoma and widespread metastatic disease.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adolescente , Carboplatina/uso terapêutico , Carcinoma/secundário , Carcinoma/cirurgia , Feminino , Raios gama/uso terapêutico , Humanos , Histerectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Ovariectomia , Paclitaxel/uso terapêutico , Papillomaviridae , Salpingectomia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
9.
Medicine (Baltimore) ; 98(32): e16490, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393352

RESUMO

RATIONALE: Pseudo progression is a noted phenomenon of immune checkpoint inhibitors therapy, which has been defined as a response after an initial enlargement of the tumor followed by tumor reduction. In July 2017, the Food and Drug Administration granted accelerated approval of nivolumab for the treatment of metastatic colorectal cancer patients whose tumor harbors deficient mismatch repair. PATIENT CONCERNS AND DIAGNOSIS: We present a patient who received nivolumab for heterogeneity of right-sided metastatic colon carcinoma. INTERVENTION: The patient was treated with nivolumab combined with chemotherapy. OUTCOME: The computed tomography showed mass lesion in the left lobe of liver remained stable while metastasis tumors under envelop of liver were exacerbated after 6 cycles of nivolumab combined with chemotherapy, and later regressed. LESSONS: The status of mismatch repair in primary tumor and metastatic liver carcinoma is contradictory but using nivolumab demonstrated encouraging efficacy. This is the first case of pseudo progression undergoing immunotherapy for heterogeneity of right-sided metastatic colon carcinoma.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Neoplasias Hepáticas/secundário , Metástase Neoplásica , Tomografia Computadorizada por Raios X
10.
Clin Nucl Med ; 44(9): e519-e521, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348077

RESUMO

A 57-year-old man with stage IIIB malignant melanoma of unknown primary presented for pretherapy FDG PET/CT that demonstrated metastatic left cervical lymph node with no other site of involvement. Following left neck dissection, nivolumab was initiated. Follow-up FDG PET/CT 3 months after initiation of nivolumab demonstrated extensive radiotracer-avid chest lymphadenopathy and multiple bone lesions. Ultrasound-guided endobronchial biopsy of the mediastinal lymph nodes demonstrated sarcoidosis.


Assuntos
Doenças Ósseas/induzido quimicamente , Pneumopatias/induzido quimicamente , Melanoma/tratamento farmacológico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Nivolumabe/efeitos adversos , Sarcoidose/induzido quimicamente , Sarcoidose/diagnóstico por imagem , Doenças Ósseas/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Pneumopatias/diagnóstico por imagem , Linfadenopatia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
11.
Medicine (Baltimore) ; 98(30): e16439, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348245

RESUMO

BACKGROUND: We performed the meta-analysis to evaluate the overall safety of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor treatment for lung cancer patients. METHOD: Randomized controlled trials were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk ratio (RR) of PD-1/PD-L1 inhibitor treatment-related death, treatment-related adverse events, any serious events, and any events leading to discontinuation were all taken into account for the final evaluation. RESULTS: Fourteen studies were collected for the meta-analysis. The RR of treatment-related death for PD-1/PD-L1 was significantly lower than that of the control group (RR = 0.37, 95% confidence interval, CI: [0.21, 0.66]). Similar analysis results could also be seen for the RR of treatment-related adverse events and adverse events leading to discontinuation. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation (RR = 1.68, 95% CI: [1.22, 3.32]). The RR of overall treatment-related adverse events was lower in nivolumab (PD-1) than that of the control group (nivolumab + ipilimumab) (RR = 0.77, 95% CI: [0.65, 0.90]). Similar analysis results could also be seen in the RR of treatment-related adverse events for grade 3 to 5 and adverse events leading to discontinuation. CONCLUSION: Compared with chemotherapy, RR of the treatment-related deaths associated with PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while it did not increase the RR when they were combined with chemotherapy or other drugs. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/mortalidade , Gradação de Tumores , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
12.
Cancer Immunol Immunother ; 68(8): 1351-1358, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31327024

RESUMO

Monoclonal antibodies targeting PD-1 are used for treating NSCLC. To date, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been poorly investigated in the oncologic field. Here, we aimed at evaluating whether serum PCSK9 might represent a predictive factor for OS in older patients with advanced NSCLC under nivolumab treatment. Among 78 patients with advanced, pre-treated NSCLC previously enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 44 patients have been included in this sub-analysis due to the availability of serum samples for the measurement of PCSK9. Before each nivolumab administration, clinical information and blood samples were collected. Median age was 71, with a prevalence of the male sex. The most represented histological type of lung cancer was adenocarcinoma. The majority of patients were former smokers (72.1%). Median PCSK9 levels were 123.59 (86.32-169.89) ng/mL and 117.17 (80.46-147.79) ng/mL at cycle 1 and 2, respectively. Based on a receiver operating characteristic curve analysis, a PCSK9 value at cycle 2 of 95 ng/mL was found as the best cutoff point for OS. Kaplan-Meier analysis demonstrated that patients below the PCSK9 cutoff (< 95 ng/mL) experienced a better OS, as confirmed by Cox proportional hazard regression analysis. In this pilot study, circulating levels of PCSK9 < 95 ng/mL at the time of the second cycle of nivolumab treatment could independently predict a better OS in elderly patients with advanced, pre-treated NSCLC. However, further studies are warranted to validate these preliminary results.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Imunoterapia/métodos , Neoplasias Pulmonares/diagnóstico , Nivolumabe/uso terapêutico , Pró-Proteína Convertase 9/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Itália , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Gan To Kagaku Ryoho ; 46(6): 1017-1026, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273168

RESUMO

The treatment of cancer has been greatly improved in recent years by immune checkpoint inhibitors. Anti-CTLA-4 and anti- PD-1 antibodies, two types of immune checkpoint inhibitors, have great potential to prolong survival, while they have different characteristics of efficacy and safety profiles. Combination therapy with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibody nivolumab has better efficacy than monotherapy. On the other hand, immune checkpoint inhibitors can result in a wide variety of immune-related adverse events(irAEs), which should be carefully managed. Such irAE includes that of the gastrointestinal tract, liver, and endocrine system, and is increased in incidence and severity when combined with ipilimumab and nivolumab. It is known that clinical characteristics of irAEs are different from those of typical autoimmune diseases. Therefore, irAEs should be managed in line with the algorithms and the appropriate use guides specifically for these drugs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1
14.
Anticancer Res ; 39(7): 3917-3921, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262921

RESUMO

AIM: To evaluate the efficacy and safety of re-treatment with anti-programmed death (PD)-L1 antibody (atezolizumab) after anti-PD-1 antibody (nivolumab/pembrolizumab) treatment in advanced non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: We retrospectively reviewed 18 NSCLC patients who received atezolizumab after anti-PD-1 antibody treatment. Data on patient characteristics, number of cycles of anti-PD-1 antibody and atezolizumab, regimens between anti-PD-1 antibody and atezolizumab, best response, and immune-related adverse events (irAEs) were collected and analyzed. RESULTS: Nine patients a had high (≥50%) PD-L1 expression. The median number of cycles of atezolizumab was 3 (range=2-7). The median progression-free survival was 2.9±1.8 months. Seven (38.9%) and 11 (61.1%) patients had stable and progressive disease, respectively. No patient achieved partial or complete response. There were no significant differences in the occurrence of irAEs between anti-PD-1 antibodies and atezolizumab. CONCLUSION: Preliminary results showed that patients previously treated with anti PD-1 antibodies received only limited benefit from subsequent atezolizumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
15.
Anticancer Res ; 39(7): 3961-3965, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262928

RESUMO

BACKGROUND/AIM: Immune check point inhibitors (ICIs) are changing cancer treatment in several malignancies, including non-small cell lung cancer (NSCLC). The introduction of these active new agents is associated with a relevant increase of costs and it is, therefore, important to create a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as overall survival (OS). This analysis was conducted to assess the pharmacological costs of first- and second-line treatments with ICIs (pembrolizumab, nivolumab and atezolizumab) for metastatic NSCLC. MATERIALS AND METHODS: The present evaluation was restricted to phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in OS. RESULTS: Six phase III RCTs were evaluated. Concerning first-line, the lowest cost per month of OS-gain was associated with the use of pembrolizumab at 2,734 €. Concerning second-line, the lowest cost per month of OS-gain was associated with the use of atezolizumab at 3,724 €. CONCLUSION: Pembrolizumab and atezolizumab are cost-effective in both first and second-line treatment for metastatic NSCLC, respectively.


Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais/economia , Antineoplásicos Imunológicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/economia , Nivolumabe/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Hinyokika Kiyo ; 65(5): 157-161, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31247693

RESUMO

A 43-year-old man underwent nephrectomy for right renal cell carcinoma (cT3aN0M1 (PUL), clear cell carcinoma). Thereafter, he was treated with sunitinib for lung metastases as the first-line therapy for three months. Because lung metastases progressed and new bone metastases appeared, nivolumab was started for the second-line treatment. Although the cancer progression was suppressed by multidisciplinary treatment combined with systemic immunotherapy and local radiation therapy, he developed severe acute kidney injury with cortical swelling after eighteen months of nivolumab treatment. A diagnosis of acute interstitial nephritis induced by nivolumab was made based on biopsy findings. Treatment with prednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function. We must consider the possibility of immunerelated adverse events, especially nivolumab-induced acute kidney injury, even after long-term treatment.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Nefrite Intersticial , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Nefrite Intersticial/induzido quimicamente , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico
17.
Rinsho Shinkeigaku ; 59(7): 431-435, 2019 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-31243249

RESUMO

A 53-year-old man suffering from squamous cell lung cancer presented with bilateral ptosis and bulbar palsy a month after initial treatment with the immune checkpoint inhibitor nivolumab. The symptoms showed worsening from midday, suggesting myasthenia gravis (MG), although anti-AChR antibody was negative. Although no muscle weakness was detected, the CK level was elevated to 5,255 IU/l, and MRI of the thigh revealed inflammation of the bilateral rectus femoris muscle. A muscle biopsy showed signs of necrotizing myopathy with expression of sarcolemmal HLA class I and accumulation of macrophages, CD4, CD8, and CD20-positive lymphocytes. Positivity for anti-titin antibody, one of the anti-striated muscle antibodies, was evident. The patient was diagnosed as having nivolumab-related necrotizing myopathy with myasthenia gravis, an immune-related adverse event (irAE). Treatment with prednisolone rapidly ameliorated the symptoms, and the serum CK level normalized. There have been several reports of nivolumab-related myositis with MG. On the basis of the muscle pathology and antibody data, we were able to clarify that necrotizing myopathy was related to the pathogenesis of this case.


Assuntos
Conectina/imunologia , Doenças Musculares/induzido quimicamente , Miastenia Gravis/induzido quimicamente , Nivolumabe/efeitos adversos , Autoanticorpos/sangue , Biomarcadores/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Necrose , Nivolumabe/uso terapêutico , Prednisolona/administração & dosagem , Músculo Quadríceps/patologia , Resultado do Tratamento
18.
Gan To Kagaku Ryoho ; 46(5): 917-920, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31189815

RESUMO

A 71-year-old woman was diagnosed with stage ⅢB locally advanced lung squamous cell cancer(cT0N3M0).Programmed death-ligand 1(PD-L1)immunostaining was negative.First -line nedaplatin plus docetaxel and second-line carboplatin plus nab-paclitaxel were followed by sequential thoracic radiation therapy(60 Gy).The patient developed radiation pneumonitis, but her condition improved with corticosteroids.However, chest computed tomography(CT)revealed multiple nodules in both lungs.Third -line carboplatin plus tegafur/gimeracil/oteracil potassium(S-1)was not successful, and fourth- line nivolumab(3mg/kg every 2weeks)was adopted.On day 9 after first administration, she developed fever and radiation recall pneumonitis.Multiple nodules rapidly formed, but they later gradually decreased in number.After 13 courses of nivolumab, the nodules had disappeared completely.Mediastinal lymph nodes decreased in size, but an abdominal lymph node remained enlarged.Nivolumab was continued, and after 24 courses, the abdominal lymph node began to shrink, and the multiple lung metastases continued to disappear.Currently, the best overall response is good partial response to nivolumab.


Assuntos
Neoplasias Pulmonares , Nivolumabe/uso terapêutico , Idoso , Antígeno B7-H1 , Células Epiteliais , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico
19.
Cancer Radiother ; 23(3): 232-239, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31147173

RESUMO

Hodgkin lymphoma is a highly curable malignancy involving lymph nodes and the lymphatic system. Even at late stage disease, about 70% of patients will be cured with standard first line therapy. For patients who experience relapse or refractory classical Hodgkin lymphoma, the standard treatment option is high-dose chemotherapy followed by autologous stem cell rescue or transplant. However about 50% of patients will have recurrence after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and have worse prognosis with median overall survival of 32% at 5 years. The anti-PD1 checkpoints inhibitors pembrolizumab and nivolumab have remarkably improved outcomes of patients with relapse of refractory classical Hodgkin lymphoma after high-dose chemotherapy followed by autologous stem cell rescue or transplantation. On the other hand, radiotherapy is an entire component of salvage therapy and its efficacy is now well established in term of local disease control in sites of relapsed or refractory Hodkin lymphoma. Defining the optimal modality and timing of radiotherapy as these new agents arrive is a challenge. An interesting approach is the combination of radiotherapy with checkpoint inhibitor and the possibility of stopping the treatment when complete response is achieved. We add to the literature two new cases of combination of radiotherapy with immunotherapy in patients who relapsed after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and consolidation with brentuximab vedotin, resulting in excellent outcomes.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Nivolumabe/uso terapêutico , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Adulto Jovem
20.
Cancer Immunol Immunother ; 68(7): 1187-1194, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31187176

RESUMO

BACKGROUND: PD-1 inhibition (PD-1i) is the standard of care in melanoma and other malignancies. In patients with bone metastases of solid tumors, the monoclonal antibody denosumab directed against RANKL is approved for the prevention of skeletal-related events. However, RANKL is not only relevant in osteoclastogenesis, but also has immunological effects. Hence, we aimed at investigating, whether the combination of PD-1i and denosumab produces synergistic effects in metastatic melanoma treatment. METHODS: We retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy. RESULTS: 29 patients were identified with a median age of 60.7 years: 20 were male and 9 were female. 20 patients (69%) were in stage IV M1c and 9 (31%) in stage IV M1d; 52% had an increased serum LDH. 24 patients (83%) received PD-1i as first-line therapy and five patients (17%) as second- or third-line therapy. 13 patients received the triple combination nivolumab, ipilimumab and denosumab (N + I+D), 16 patients received PD-1i and denosumab (PD-1i + D). Within a median follow-up time of 19.8 months, 17 patients progressed with a median time to progression of 6 months. The objective response rate was 54% in the N + I + D group and 50% in the PD-1i + D group. Recalcification of bone metastases was radiologically observed in 18 (62%) patients. No unexpected treatment-related adverse events emerged. CONCLUSIONS: The combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Denosumab/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Denosumab/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Ligante RANK/antagonistas & inibidores , Ligante RANK/imunologia , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA