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4.
Nihon Shokakibyo Gakkai Zasshi ; 118(8): 768-774, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34373396

RESUMO

A 90-year-old woman diagnosed with stage IV gastric cancer (pT4a[SE]N2M1 [P, CY1]) after distal gastrectomy for her tarry stool was treated with S-1 monotherapy for 7 months, nab-PTX monotherapy for 3 months, and wPTX+RAM therapy for 3 months. Ascending colon tumor was revealed as peritoneal recurrence treated via right hemicolectomy. The nivolumab therapy was started as the fourth treatment. As the tumor progressed, sIL-2R, a destruction product of regulatory T cell surface antigens, tended to increase and the lymphocyte count tended to decrease, with the sIL-2R/lymphocyte count ratio changing in parallel with CA19-9. Throughout the course after gastrectomy, NLR increased and LMR decreased as the tumor status and general condition worsened.


Assuntos
Nivolumabe , Neoplasias Gástricas , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Linfócitos , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
5.
In Vivo ; 35(5): 2855-2862, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410978

RESUMO

BACKGROUND/AIM: The relationship between albumin-to-alkaline phosphatase ratio (AAPR) and the outcome of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors remains unresolved. We aimed to clarify the prognostic role of AAPR in nivolumab monotherapy for previously treated mRCC. PATIENTS AND METHODS: We retrospectively evaluated 60 patients with mRCC treated with nivolumab after failure of at least one molecular targeted therapy. The patients were stratified into two groups based on the baseline AAPR. The threshold of AAPR was determined using receiver-operating characteristics and Youden index analyses. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of nivolumab therapy were compared between the high and low AAPR groups. RESULTS: The threshold of AAPR was set at 0.3, and 20 patients (33%) were assigned to the low AAPR group. The median OS and PFS were significantly lower in the low AAPR group than those in the high group (OS: 8.3 months vs. not reached, p<0.0001; PFS: 2.9 vs. 10.4 months, p=0.0006). Moreover, ORR was significantly lower in the low AAPR group than in the high group (16% vs. 45%, p=0.0397). Multivariate analyses further showed that AAPR was an independent factor for OS [HR=0.27 (95% CI=0.09-0.77), p=0.0151] but not for PFS (p=0.174). CONCLUSION: Baseline AAPR was significantly associated with outcome in patients with mRCC receiving nivolumab monotherapy and may, therefore, constitute an effective prognostic factor for nivolumab treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Albuminas , Fosfatase Alcalina , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos
6.
Hinyokika Kiyo ; 67(7): 309-312, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34353011

RESUMO

We report a case of Stauffer syndrome-like findings in a patient with metastatic renal carcinoma treated by surgery and molecular targeted therapy. The patient was a 58-year-old woman diagnosed with renal carcinoma with multiple metastases. She had hepatosplenomegaly and hepatic dysfunction with elevated serum liver enzyme and IL-6 levels. Treatment with temsirolimus and axitinib reduced the size of the local and metastatic tumors and simultaneously improved the hepatosplenomegaly. The local tumor was excised by laparoscopic nephrectomy, treated with axitinib and then with nivolumab. With the reduction in the metastatic tumor size, serum liver enzyme and IL-6 levels decreased. It was suggested that molecular targeted therapy is an effective treatment when the findings of metastatic renal cell carcinoma, are similar to those of Stauffer syndrome.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Nivolumabe/uso terapêutico
7.
J Med Case Rep ; 15(1): 345, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34256852

RESUMO

BACKGROUND: Primary malignant melanoma of the esophagus is a rare form of mucosal melanoma with a poor prognosis. While immune checkpoint inhibitors have recently extended overall survival in metastatic melanoma, data on their effects on primary malignant melanoma of the esophagus are limited because of its rarity. Here, we report the first case of long-term complete remission of metastatic primary malignant melanoma of the esophagus after nivolumab monotherapy. CASE PRESENTATION: A 79-year-old Asian man with a history of prostate cancer, gallbladder cancer, deep vein thrombosis, hypertension, and diabetes mellitus presented with gross hematuria. Cystoscopy revealed a solitary tumor on the right posterior wall of the bladder, and transurethral resection of bladder tumor was performed. Pathology was consistent with metastatic melanoma. A pigmented submucosal tumor-like growth in the esophagus was discovered on esophagogastroduodenoscopy. Computed tomography showed widespread metastases. The patient was diagnosed as having primary malignant melanoma of the esophagus with metastases to the stomach, subcutaneous tissue, lung, bladder, pleura, and peritoneum. Complete remission was achieved after seven cycles of triweekly nivolumab monotherapy. While nivolumab was discontinued because of kidney injury, the patient has remained tumor-free for over 4 years without further treatment. CONCLUSION: Immune checkpoint inhibitors may have astonishing curative effects in selected populations. More research is warranted to identify factors that increase the likelihood of achieving complete remission in primary malignant melanoma of the esophagus as well as in other melanomas.


Assuntos
Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Idoso , Esôfago , Humanos , Masculino , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico
8.
Gan To Kagaku Ryoho ; 48(7): 963-965, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267037

RESUMO

The prognosis of patients with brain metastasis is very poor. Very few cases of combined treatment with nivolumab(240 mg/body, day 1, q2w, a programmed cell death-1[PD-1]inhibitor)and gamma knife radiosurgery(GKR)(27 Gy/3 Fr) for gastric cancer patients with brain metastasis have been reported. Here, we discuss the case of a 55-year-old man with HER2-positive poorly differentiated gastric adenocarcinoma with multiple bone and intra-abdominal lymph node metastases. After 25 courses of SOX(oxaliplatin 100 mg/m2, day 1, q3w plus S-1 120 mg/day, day 1-14, po, q3w)plus trastuzumab( 6 mg/kg, q3w)treatment, brain metastasis was detected. Subsequently, combined treatment with GKR and nivolumab(8 courses, anti-PD-1 monotherapy)was initiated. Both intra-abdominal and brain lesions decreased in response to this treatment, showing that combined therapy with nivolumab and GKR could be effective for treating gastric cancer patients with brain metastasis.


Assuntos
Adenocarcinoma , Neoplasias Encefálicas , Radiocirurgia , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
9.
Lung Cancer ; 158: 146-150, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34217967

RESUMO

IMPORTANCE: Therapies targeting immune checkpoints, such as the programmed cell death 1 (PD-1) receptor, have become the standard-of-care for patients with non-small cell lung cancer (NSCLC), but people living with HIV (PLWH) were excluded from these studies. OBJECTIVE: To evaluate the efficacy and tolerability of nivolumab in PLWH with advanced NSCLC. DESIGN: The CHIVA2 study was a nonrandomized, open-label, phase 2 clinical trial in PLWH with previously treated advanced NSCLC. SETTING: National multicenter prospective study. PARTICIPANTS: patients had viral load of <200 copies/mL, regardless of their CD4+ T-cell count. INTERVENTION: Nivolumab was administered in second or third line, as monotherapy intravenously at 3 mg/kg every 2 weeks, until disease progression or limiting toxicity. MAIN OUTCOMES AND MEASURES: The primary endpoint was disease control rate, evaluated using the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Sixteen patients with advanced NSCLC were enrolled: 14 (88 %) were men, median age was 58 years (range: 44-71), and all were smokers. The median duration of nivolumab treatment was 3.5 months (range: 0.5-26.5). The median follow-up was 23.6 months. Disease control rate was 62.5 % for 15 evaluable patients at 8 weeks (2 with partial response, 8 with stable disease, and 5 with disease progression). Twelve (75 %) patients had treatment-related adverse events, which were mild or moderate, except for one patient experiencing severe pruritus, onycholysis, and pemphigoid. There were no opportunistic infections or unexpected immune-related events. HIV viral load was stable during treatment. An increase in proliferating CD8+ and CD4+ T-cells was observed after 3 nivolumab cycles in a subgroup of 9 patients. CONCLUSIONS AND RELEVANCE: Second/third-line nivolumab treatment was well-tolerated and beneficial in PLWH with NSCLC. Future trials should investigate immune checkpoint inhibitors in first-line settings. TRIAL REGISTRATION: EudraCT.ema.europa.eu registration number: 2016-003796-22.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por HIV , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos
10.
Anticancer Res ; 41(8): 3925-3931, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281855

RESUMO

BACKGROUND/AIM: This study clarified the predictive impact of serum biomarkers on therapeutic sensitivity to nivolumab in patients with gastric cancer (GC). PATIENTS AND METHODS: The outcomes of 27 patients who received nivolumab to treat postoperative recurrent or unresectable advanced GC were reviewed. Blood testing was performed immediately before and after two courses of nivolumab. We also focused on the rate of change of each blood variable. RESULTS: The decrease in albumin (Alb) levels (p=0.035) and increase in lactate dehydrogenase (LDH) levels (p=0.012) after two courses of nivolumab were significantly larger in patients with disease progression. Furthermore, therapeutic resistance was significantly associated with an elevated LDH-to-Alb ratio (LAR) after two courses of nivolumab. CONCLUSION: Decreased Alb or increased LDH levels after two courses of nivolumab predicted nivolumab sensitivity in patients with GC. An increased LAR was a meaningful predictor of nivolumab resistance.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , L-Lactato Desidrogenase/sangue , Nivolumabe/uso terapêutico , Albumina Sérica/análise , Neoplasias Gástricas/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/farmacologia , Biomarcadores/sangue , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Nivolumabe/farmacologia , Prognóstico , Neoplasias Gástricas/sangue
11.
Anticancer Res ; 41(7): 3673-3682, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230166

RESUMO

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.


Assuntos
Inflamação/patologia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
12.
J Dtsch Dermatol Ges ; 19(8): 1186-1198, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34255435

RESUMO

BACKGROUND: Anti-programmed death 1 (PD-1) antibodies have evolved as a new standard of care in the adjuvant treatment of completely resected melanoma. Real-world data on treatment efficacy and safety as well as cost-effectiveness are still limited. PATIENTS AND METHODS: Treatment outcomes were retrospectively analyzed in a continuous patient cohort receiving adjuvant nivolumab (91 patients) or pembrolizumab (9 patients). Based on the obtained clinical data, a semi-Markov model was developed to evaluate cost-effectiveness. RESULTS: After a median follow-up of 11.5 months, disease recurrence was observed in 39 patients (39 %). The site of first recurrence was locoregional in 17, distant in 19, and combined locoregional and distant in three patients. Twelve-month estimates for recurrence- and distant-metastasis-free survival were 64.8 % and 77.4 %, respectively. Sixteen patients experienced grade 3 or 4 treatment-related adverse events, while 22 patients discontinued treatment due to adverse events. The base-case Markov model yielded an incremental cost-effectiveness ratio of 13,330 € per quality-adjusted life year for adjuvant anti-PD-1 antibody treatment compared to a simulated observation cohort. CONCLUSIONS: Real-world outcomes of adjuvant anti-PD-1 antibody therapy in completely resected melanoma appear comparable to clinical trial data. Moreover, our data suggests this treatment strategy to be cost-effective according to Austrian health economic standards.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
13.
Adv Ther ; 38(7): 3962-3972, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34100243

RESUMO

INTRODUCTION: The effectiveness of nivolumab plus ipilimumab with two cycles of chemotherapy (NIC) for advanced non-small cell lung cancer (NSCLC) has been demonstrated. We aimed to evaluate the cost-effectiveness of NIC for advanced NSCLC from the US payer perspective. METHODS: A Markov model has been established to predict the disease course of previously untreated advanced NSCLC. The clinical data were derived from the CheckMate 9LA trial. Cost and utility were obtained from the literature. Model outputs included the incremental cost-effectiveness ratios (ICERs), incremental monetary benefit (INMB), and incremental net-health benefit (INHB). A series of sensitivity analyses were performed to analyze the uncertainty of the model. RESULTS: Our results showed that NIC versus chemotherapy alone cost $264,278 and yielded an additional 0.80 quality-adjusted life-years (QALYs), which led to an ICER of $202,275/QALY gained. The INHB was - 0.28 QALY, and the INMB was - $41,865 at the threshold of $150,000/QALY. The results of one-way sensitivity analysis showed that the hazard ratio of overall survival was the most sensitive parameter. CONCLUSION: NIC was unlikely to be cost-effective as a first-line treatment for patients with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Análise Custo-Benefício , Humanos , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida
14.
Medicine (Baltimore) ; 100(19): e25773, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106609

RESUMO

RATIONALE: Anti-PD-1 antibody is the standard therapy for treatment-resistant gastric cancer, but only a limited number of patients respond. Additionally, cases of hyper-progressive disease (HPD) in which tumor growth accelerates after anti-PD-1 antibody administration have been reported; however, the biological mechanism has not been elucidated. PATIENT CONCERNS: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment. DIAGNOSIS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD. INTERVENTIONS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy. OUTCOMES: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens. LESSONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Macrófagos Associados a Tumor/efeitos dos fármacos , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Progressão da Doença , Evolução Fatal , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia
15.
Medicine (Baltimore) ; 100(19): e25862, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106633

RESUMO

RATIONALE: Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy. PATIENT CONCERNS: A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia. DIAGNOSES: A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis. INTERVENTIONS: The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area. OUTCOMES: Disease progression finally led to the patient's death 3 years after diagnosis. LESSONS: This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Melanoma/terapia , Neoplasias Meníngeas/terapia , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Humanos , Laminectomia/métodos , Masculino , Melanócitos/patologia , Melanoma/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem
16.
J Transl Med ; 19(1): 232, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059094

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients. METHODS: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy. DISCUSSION: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&draw=2&rank=1 .


Assuntos
Mesotelioma Maligno , Mesotelioma , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Ipilimumab/uso terapêutico , Mesotelioma/tratamento farmacológico , Nivolumabe/uso terapêutico , Vacinação
17.
In Vivo ; 35(4): 2247-2251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182503

RESUMO

BACKGROUND: Multimodality treatment including immune check point inhibitors is required for stage IV oesophagogastric junction cancer (OGJC). CASE REPORT: A 69-year-old man, was diagnosed with advanced OGJC and para-aortic lymph node metastasis (T3N+M1, stage IV), which upon biopsy, was shown to be an adenocarcinoma. After eight courses of nivolumab as third-line chemotherapy, the primary tumour and enlarged regional and para-aortic lymph nodes shrunk markedly, while tumour markers decreased within normal ranges. We performed a minimally invasive Ivor-Lewis oesophagectomy with completion of an abdominal D2 and transhiatal lower mediastinal lymph node dissection. Pathological findings revealed a complete response for the primary tumour and a regional lymph node metastasis. A biopsy of the previous sample revealed microsatellite instability-negativity, Epstein-Barr virus-negativity, and programmed cell death-1-ligand combined positive score of 2. He was followed up for 3 months without recurrence. CONCLUSION: Nivolumab may induce pathological complete response for stage IV OGJC even in cases negative for microsatellite instability and Epstein-Barr virus, besides the programmed cell death-1-ligand combined positive score of <5.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esofagectomia , Junção Esofagogástrica/cirurgia , Herpesvirus Humano 4 , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
18.
Nat Commun ; 12(1): 4031, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188042

RESUMO

The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/patologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Glioblastoma/patologia , Humanos , Ipilimumab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Resultado do Tratamento , Microambiente Tumoral/imunologia
19.
N Engl J Med ; 384(22): 2102-2114, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34077643

RESUMO

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Placebos/uso terapêutico , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
20.
Hinyokika Kiyo ; 67(5): 197-203, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34126663

RESUMO

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Axitinibe , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Duodeno , Humanos , Ipilimumab/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Masculino , Recidiva Local de Neoplasia , Nefrectomia , Nivolumabe/uso terapêutico , Pâncreas , Trombectomia , Veia Cava Inferior
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