Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.315
Filtrar
1.
Anticancer Res ; 42(5): 2727-2735, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35489743

RESUMO

BACKGROUND/AIM: CheckMate 214 study revealed that nivolumab plus ipilimumab combination therapy showed a strong and durable effect compared to sunitinib for patients with advanced renal cell carcinoma (aRCC). Most of the patients underwent previous nephrectomy before systemic treatment. We retrospectively investigated the clinical outcomes of Japanese patients treated with cytoreductive nephrectomy following nivolumab plus ipilimumab for aRCC. PATIENTS AND METHODS: Seventy-nine patients were treated with systemic therapy for aRCC between October 2018 and August 2021 at the Saitama Medical University International Medical Center. Ten of 61 patients treated with nivolumab plus ipilimumab underwent cytoreductive nephrectomy after the combined immunotherapy. RESULTS: The median overall survival and progression-free survival were 24.3 and 15.9 months, respectively. The objective response rate was 50.8%; 9.8% of patients had a complete response, and the median time to objective response was 3.2 (range=1.3-19.7) months. The estimated percentage of patients who sustained an objective response at 30 months was 73.0%. Twenty-three patients (74%) in the complete or partial response (CR/PR) group, 11 patients (52%) in the stable disease (SD) group, and two patients (22%) in the progressive disease (PD) group had immune-related adverse events of grade 3 or higher, respectively. For all 10 patients, cytoreductive nephrectomy following nivolumab plus ipilimumab treatment were completed safely. Three patients achieved a pathological complete response without viable cancer cells. Only two patients had residual lesions on images after deferred cytoreductive nephrectomy; the remaining patients achieved radiological CR. CONCLUSION: Cytoreductive nephrectomy after nivolumab plus ipilimumab treatment could be useful in a limited number of cases, possibly resulting in curative nephrectomy due to the durable therapeutic effect of immunotherapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/etiologia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Ipilimumab/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Masculino , Nefrectomia , Nivolumabe/efeitos adversos , Estudos Retrospectivos
2.
Int J Biol Sci ; 18(7): 2775-2794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541908

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal tumors in China and worldwide, although first-line therapies for HCC, such as atezolizumab and bevacizumab, have been effective with good results, the researches on new therapies have attracted much attention. With the deepening research on tumor immunology, the role and operation mechanism of immune cells in the tumor microenvironment (TME) of HCC have been explained, such as programmed cell death protein 1 (PD-1) binding to ligand could cause T cell exhaustion and reduce IFN-γ T cell secretion, cytotoxic T lymphocyte 4 (CTLA-4) and CD28 mediate immunosuppression by competing for B7 protein and disrupting CD28 signal transduction pathway, which also lays the foundation for the development and application of more new immune checkpoint inhibitors (ICIs). The biological behavior of various immune checkpoints has been proved in HCC, such as PD-1, programmed cell death ligand 1 (PD-L1), CTLA-4 and so on, leading to a series of clinical trials. Currently, FDA approved nivolumab, pembrolizumab and nivolumab plus ipilimumab for the treatment of HCC. However, the treatment of ICI has the disadvantages of low response rate and many side effects, so the combination of ICIs and various other therapies (such as VEGF or VEGFR inhibition, neoadjuvant and adjuvant therapy, locoregional therapies) has been derived. Further studies on immune checkpoint mechanisms may reveal new therapeutic targets and new combination therapies in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Antígeno B7-H1/metabolismo , Antígenos CD28/uso terapêutico , Antígeno CTLA-4/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Imunoterapia/métodos , Ligantes , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/uso terapêutico , Microambiente Tumoral
4.
J Drugs Dermatol ; 21(5): 529-530, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533039

RESUMO

Nivolumab (anti PD-1 antibody) and ipilimumab (anti CTLA-4 antibody) are immune checkpoint inhibitors (ICI) that effectively stimulate the native T cell response and lead to an antitumor response. The medications have been approved for the treatment of metastatic melanoma. However, ICIs are associated with higher risk for cutaneous immune-related adverse events (irAEs). Although most of the adverse events present as maculopapular rash, some patients develop Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis which are dermatologic emergencies with high mortality. We report a fatal case of SJS associated with nivolumab and a non-fatal case of TEN with nivolumab/ipilimumab combination therapy in patients with metastatic melanoma. It is also not unusual to develop SJS or TEN after weeks or months on checkpoint inhibitor therapy. Given the high rate for mortality, dermatologists and other clinicians should closely follow any rash from these immunotherapies due to the risk for future development of SJS or TEN. J Drugs Dermatol. 2022;21(5):529-530. doi:10.36849/JDD.6559.


Assuntos
Exantema , Melanoma , Síndrome de Stevens-Johnson , Exantema/induzido quimicamente , Humanos , Ipilimumab/efeitos adversos , Melanoma/patologia , Nivolumabe/efeitos adversos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia
5.
Front Immunol ; 13: 871452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493494

RESUMO

Since the first approval of immune checkpoint inhibitors (ICIs) in 2011, these agents have rapidly become an integral treatment option across tumor types. However, with the increased adoption of ICIs, the incidence of immune-related adverse events (irAEs) continues to rise, and rare toxicity continues to be reported. Here, we present a case of a 70-year-old male patient with widespread metastatic melanoma who developed rapid onset anasarca and transaminitis after initiation of dual anti-PD-1/CTLA-4 inhibition with nivolumab and ipilimumab. An extensive workup was performed with serologies returning positive for anti-tissue transglutaminase immunoglobulin (tTG-IgA) and endoscopy revealing duodenal mucosal atrophy with duodenal biopsies confirming celiac disease. All symptoms resolved after initiation of a gluten-free diet without the addition of immunosuppression. This case highlights the importance of considering celiac disease in patients with suspected protein-losing enteropathy on ICI, the fulminant nature this uncommon irAE can present with, and underscores the broad differential clinicians must maintain when managing presumed irAEs.


Assuntos
Doença Celíaca , Melanoma , Idoso , Doença Celíaca/diagnóstico , Terapia Combinada , Humanos , Ipilimumab/efeitos adversos , Masculino , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos
6.
Front Immunol ; 13: 871217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514990

RESUMO

A man in his early 50s presented with small bowel obstruction, requiring emergency laparoscopic small bowel resection for the metastatic melanoma of the jejunum with no identifiable primary lesion. One week after his first treatment with ipilimumab and nivolumab, he presented with diffuse abdominal pain, constipation, and fatigue. A computerized tomography scan did not identify a cause for his symptoms. This was rapidly followed by thrombocytopenia on day 11 and then anemia. He commenced intravenous corticosteroids for a suspected diagnosis of immune-related thrombocytopenia. On day 15, a generalized onset motor seizure occurred, and despite plasmapheresis later that day, the patient died from fatal immune-related thrombotic thrombocytopenic purpura (TTP). This was confirmed with suppressed ADAMTS13 (<5%) testing on day 14. Immune-related TTP is a rare and, in this case, fatal immune- related adverse event. Further studies are required to identify additional immunosuppressive management for immune-related TTP.


Assuntos
Melanoma , Segunda Neoplasia Primária , Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Humanos , Fatores Imunológicos , Imunoterapia , Ipilimumab/efeitos adversos , Masculino , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Púrpura Trombocitopênica Trombótica/diagnóstico
7.
J Immunother Cancer ; 10(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35383114

RESUMO

BACKGROUND: Retrospective studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving immune checkpoint inhibitors (ICIs). We compared the incidence of HPD during treatment with nivolumab±ipilimumab versus natural tumor progression with placebo in post hoc analyses of two randomized, double-blind clinical trials. METHODS: ATTRACTION-2 randomized patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) and progression on ≥2 prior regimens to nivolumab 3 mg/kg Q2W or placebo. CheckMate 451 randomized patients with extensive-disease small cell lung cancer (ED SCLC) and ongoing complete/partial response or stable disease after first-line chemotherapy to nivolumab 240 mg Q2W, nivolumab 1 mg/kg+ipilimumab 3 mg/kg Q3W for four doses then nivolumab 240 mg Q2W, or placebo. Patients receiving ≥1 dose of study drug and with tumor scans at baseline and the first on-treatment evaluation were included in the HPD analyses. HPD definitions were ≥20%, ≥50%, and ≥100% increase in target lesion sum of the longest diameters (SLD) at the first on-treatment assessment. RESULTS: In the ATTRACTION-2 HPD-evaluable population, 243 patients received nivolumab and 115 placebo. Fewer patients receiving nivolumab versus placebo had increases in SLD ≥20% (33.7% vs 46.1%) and ≥50% (6.2% vs 11.3%); similar proportions had increases in SLD ≥100% (1.6% vs 1.7%). In the CheckMate 451 HPD-evaluable population, 177 patients received nivolumab, 179 nivolumab+ipilimumab, and 175 placebo. Fewer patients receiving nivolumab or nivolumab+ipilimumab versus placebo had increases in SLD ≥20% (27.1%, 27.4% vs 45.7%), ≥50% (10.2%, 11.2% vs 22.3%), and ≥100% (2.8%, 2.8% vs 6.3%). CONCLUSIONS: Nivolumab±ipilimumab was not associated with an increased rate of progression versus placebo in patients with GC, GEJC, or ED SCLC, suggesting that previous reports of HPD may reflect the natural disease course in some patients rather than ICI-mediated progression. TRIAL REGISTRATION NUMBER: NCT02538666; NCT02267343.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/patologia , Nivolumabe/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
8.
BMC Cancer ; 22(1): 418, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428212

RESUMO

BACKGROUND: Immune-check point inhibitors (ICPIs) for treatment of cancer patients sometimes induce potentially life-threatening immune-related adverse events (irAEs), which predict ICPIs treatment efficacy. Prediction of irAEs would be useful for management of irAEs and prediction of ICPIs efficacy. This study aimed to determine predictors of irAEs in patients with recurrent or unresectable advanced gastric cancer (RUGC) treated with nivolumab. METHODS: Seventy-eight RUGC patients treated with nivolumab at nine institutions between January 2017 and April 2020 were included in this study. The usefulness of specific blood test results as predictors of irAEs was evaluated. RESULTS: We observed irAEs in 15 (19.2%) patients. The disease control rate was significantly higher in the patients with irAEs than in those without (86.7% vs. 42.9%; P < 0.001). The median progression-free survival was significantly longer for patients with irAEs than for patients without (4.9 vs. 2.6 months; P = 0.018). The median survival time was longer for patients with irAEs than for those without (9.4 vs. 5.8 months; P = 0.041). The receiver operating characteristic (ROC) curves for irAEs indicated that the area under the curve (AUC) of carbohydrate antigen 19-9 (CA19-9) was highest (0.692; P = 0.022), followed by that for the platelet count × serum C-reactive protein (P-CRP) value (0.680; P = 0.032). The AUC for the CA19-9 + P-CRP combination was 0.782, which was more useful than that for either component and significantly associated with overall survival of nivolumab-treated RUGC patients. CONCLUSIONS: The CA19-9 + P-CRP combination was predictive of irAEs and prognosis in RUGC patients.


Assuntos
Neoplasias Pulmonares , Neoplasias Gástricas , Proteína C-Reativa , Antígeno CA-19-9 , Humanos , Recidiva Local de Neoplasia , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
9.
Lung Cancer ; 167: 8-16, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367910

RESUMO

OBJECTIVE: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). MATERIALS AND METHODS: Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. RESULTS: Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy. CONCLUSIONS: Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etiologia , Mesotelioma/tratamento farmacológico , Nivolumabe/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida
10.
Eur J Cancer ; 167: 70-80, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35395553

RESUMO

BACKGROUND: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). METHODS: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. RESULTS: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8-5.6) than patients with CM (10.1 months; 95%CI: 8.5-12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26-2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15-2.06; P = 0.004) than CM. CONCLUSIONS: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Cutâneas , Estudos de Coortes , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/mortalidade , Nivolumabe/efeitos adversos , Estudos Prospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia
12.
Lancet Oncol ; 23(5): 612-624, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35390339

RESUMO

BACKGROUND: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups. METHODS: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment. FINDINGS: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib. INTERPRETATION: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma. FUNDING: Bristol Myers Squibb, ARTIC.


Assuntos
Carcinoma de Células Renais , Nivolumabe , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Ipilimumab , Lipase , Masculino , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Sunitinibe , Microambiente Tumoral
13.
Gastric Cancer ; 25(3): 619-628, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35254550

RESUMO

BACKGROUND: Nivolumab monotherapy has demonstrated superior efficacy in advanced unresectable gastric cancer (GC), but its impact on resectable GC remains unknown. This phase I study aimed to evaluate safety, feasibility, and potential biomarkers of neoadjuvant nivolumab monotherapy in resectable GC. METHODS: Untreated, resectable, cT2 or more advanced gastric adenocarcinomas with clinical stage I, II, or III were treated with two doses of nivolumab before gastrectomy. Patients were excluded if their tumors may be applicable to neoadjuvant chemotherapy. The primary endpoint was the incidence of adverse event (AE) categories of special interest. RESULTS: All of the 31 enrolled patients completed 2 doses of nivolumab monotherapy. While 30 (97%) patients underwent surgery with curative intent, 1 patient discontinued before the planned surgical intervention because of a newly emerging liver metastasis. Seven patients (23%) had nivolumab treatment-related AEs, and one patient had a treatment-related AE of grade 3-4. The incidences of treatment-related AE categories of special interest ranged from 0 to 6%. Notable surgical complications included two cases of grade 3 anastomotic leakage and two cases of pancreatic fistula. The major pathologic response (MPR) assessed by the independent pathology review committee was achieved in five (16%) patients, of which one patient had a pathologic complete response. The MPR was mostly observed in patients with positive PD-L1 expression, high microsatellite instability, and/or high tumor mutation burden. CONCLUSIONS: Neoadjuvant nivolumab monotherapy is feasible with an acceptable safety profile and induces a MPR in certain patients with resectable GC. (Registration: clinicaltrials.jp, JapicCTI-183895).


Assuntos
Adenocarcinoma , Nivolumabe , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Humanos , Instabilidade de Microssatélites , Terapia Neoadjuvante/efeitos adversos , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
14.
Curr Oncol Rep ; 24(6): 695-702, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35247142

RESUMO

PURPOSE OF REVIEW: Four immuno-oncology (IO)-based combinations have demonstrated overall survival benefit as frontline treatment of metastatic clear cell renal cell carcinoma (mccRCC). Choosing among the available combinations depends on treating physician's interpretation of existing data without level I evidence to inform choice of therapy. Landmark trials of mccRCC are reviewed and perspective on treatment options is provided. RECENT FINDINGS: The four IO-based combinations reviewed are ipilimumab/nivolumab (IO/IO), pembrolizumab/axitinib (IO/TKI), nivolumab/cabozantinib (IO/TKI), and pembrolizumab/lenvatinib (IO/TKI). The ipilimumab/nivolumab combination is notable for durable efficacy after extended 4-year follow-up. IO/TKI combinations have clinical efficacy across all IMDC risk groups with higher response rates and longer progression-free survival (PFS) but also had higher ≥ grade 3 adverse events rate. Patient tumor burden, performance status, and IMDC risk group are factors in choosing an IO-based treatment. IO/IO and IO/TKI combinations for mccRCC have distinct efficacy and toxicity profiles. Future studies are needed to identify biomarkers to optimize patient outcomes.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/secundário , Feminino , Humanos , Ipilimumab/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico
15.
Sci Rep ; 12(1): 3669, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256688

RESUMO

It has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find factors that could be useful biomarkers for the diagnosis. A single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro-granulomas was also evaluated. The frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p = 0.00112). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p < 0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than those in AIH or DILI patients (p < 0.05). We demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Hepatite A , Hepatite , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Granuloma/induzido quimicamente , Hepatite/patologia , Humanos , Inflamação , Neoplasias Pulmonares/patologia , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos
16.
Pediatrics ; 149(4)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35274131

RESUMO

Immune checkpoint inhibitor (ICI) therapies are now first-line therapy for many advanced malignancies in adults, with emerging use in children. With increasing ICI use, prompt recognition and optimal management of ICI-associated immune-related adverse events (IRAEs) are critical. Nearly 60% of ICI-treated adults develop IRAEs, which commonly manifest as autoimmune skin, gastrointestinal, and endocrine disease and can be life-threatening. The incidence, presentation, and disease course of spontaneous autoimmune diseases differ between adults and children, but the pattern of pediatric IRAEs is currently unclear. We report a case of a pediatric patient presenting with new onset autoimmune diabetes mellitus and diabetic ketoacidosis during ICI treatment of fibrolamellar hepatocellular carcinoma (FLC). Distinct from spontaneous type 1 diabetes mellitus (T1DM), this patient progressed rapidly and was negative for known ß cell autoantibodies. Additionally, the patient was positive for 21-hydroxylase autoantibodies, suggesting development of concomitant adrenal autoimmunity. Current guidelines for the management of IRAEs in adults may not be appropriate for the management of pediatric patients, who may have different autoimmune risks in a developmental context.


Assuntos
Doenças Autoimunes , Autoimunidade , Diabetes Mellitus , Cetoacidose Diabética , Interferon-alfa , Neoplasias , Nivolumabe , Poliendocrinopatias Autoimunes , Adulto , Criança , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/terapia , Humanos , Interferon-alfa/efeitos adversos , Nivolumabe/efeitos adversos
17.
Prague Med Rep ; 123(1): 35-42, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35248163

RESUMO

Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity - hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.


Assuntos
Linfo-Histiocitose Hemofagocítica , Melanoma , Humanos , Imunoterapia , Ipilimumab/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos
18.
Nature ; 603(7903): 942-948, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322232

RESUMO

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1 , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Seguimentos , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico
19.
Dermatol Ther ; 35(5): e15432, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35266258

RESUMO

The widespread use of PD-1 inhibitors to treat various solid tumors has brought certain challenges for the clinician, including immune-related adverse events (irAEs). Cutaneous toxicities are among the most observed irAEs. Bullous and lichenoid dermatoses following PD-1 inhibitor therapy have been described. Here we report a novel case of lichen planus pemphigoides, featuring characteristics of both bullous pemphigoid and lichen planus, in a patient treated with nivolumab for renal cell carcinoma. We subsequently review all three cutaneous conditions which may arise in the context of PD-1 inhibitor therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Líquen Plano , Erupções Liquenoides , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Líquen Plano/induzido quimicamente , Líquen Plano/diagnóstico , Líquen Plano/tratamento farmacológico , Erupções Liquenoides/induzido quimicamente , Erupções Liquenoides/diagnóstico , Masculino , Nivolumabe/efeitos adversos
20.
Anticancer Res ; 42(3): 1433-1437, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220236

RESUMO

BACKGROUND/AIM: Immunotherapy with PD-1/PDL1 blocking monoclonal antibodies has improved survival compared to the standard-of-care chemotherapy for several malignancies at different stages of these malignancies. Due to several reasons, many cancer patients in medical need have no access to these drugs. In this study, we aimed to investigate whether a low dose of nivolumab could also lead to a therapeutic response. PATIENTS AND METHODS: Patients with advanced cancer were treated with a flat low dose of 10 mg of nivolumab IV every two weeks at no drug cost. RESULTS: Disease control was noted in nine of the 18 patients. Two patients achieved complete remission, two had prolonged partial remission, and five had stable disease, of these only two experienced adverse events. CONCLUSION: A flat low dose of nivolumab may have clinical activity and is a cheap therapeutic option in patients in medical need for whom standard-dose immune checkpoint inhibitors are not accessible for any reason.


Assuntos
Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/economia , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/imunologia , Neoplasias/patologia , Nivolumabe/efeitos adversos , Nivolumabe/economia , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...