Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Anticancer Drugs ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387593

RESUMO

Several novel androgen receptor (AR)-inhibitors have been introduced for nonmetastatic castration-resistant prostate cancer (nmCRPC) treatment, with the improvement of survival outcomes which need to be balanced against the risk of adverse events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating enzalutamide, apalutamide and darolutamide in nmCRPC patients, to assess overall survival (OS), incidence and risk of adverse drug events, adverse-events-related death and adverse-events-related treatment discontinuation. We selected three RCTs (SPARTAN, PROSPER and ARAMIS). New hormonal agents administration resulted in better OS, despite the increased risk of several any grade and grade 3-4 adverse events. In the decision-making process, careful evaluation of expected adverse events, patients' comorbidities and maintenance of quality of life are mandatory.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34058953

RESUMO

Introduction: Substantial paradigm shifts have been recently registered in metastatic renal cell carcinoma (mRCC), with combination therapies including immunotherapy showing unprecedented results. We performed number needed to treat (NNT) and number needed to harm (NNH) analyses to evaluate these approaches in mRCC.Areas covered: Clinical data of mRCC patients enrolled in four phase III trials were collected. The rates at 6, 12, 18, and 24 months for overall survival (OS), duration of response (DoR), and progression-free survival (PFS) were considered. At 6 months, the number of patients that should be treated to prevent one death with sunitinib was 20 for both pembrolizumab-lenvatinib or axitinib, 14 for nivolumab-cabozantinib, and 50 for nivolumab-ipilimumab. NNT was 100 (at 6 months) or >100 (at 12 and 18 months) for nivolumab-ipilimumab. The combinations reported peculiar and not superimposable safety profiles at the NNH analysis.Expert opinion: Although our results should be interpreted with caution, the analysis provides useful insight into the increasingly compelling interpretation of clinical trials. Immune combinations present clinically meaningful differences in terms of efficacy, with some treatments reporting different results at the NNT and the NNH analyses.

3.
Eur J Cancer ; 150: 99-107, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33892411

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non-small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography ([18F]FDG-PET/CT)-derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. MATERIALS AND METHODS: This is a monocentric retrospective cohort study including patients with advanced NSCLC (stage IV) and Programmed death-ligand 1 (PD-L1) expression ≥50% treated with pembrolizumab. A control group of patients treated with epidermal growth factor receptor (EGFR) inhibitors for EGFR-mutated NSCLC was also enrolled. Only patients with a positive [18F]18F-FDG PET/CT result within 60 days from treatment initiation were included.Total metabolic tumour volume (tMTV) was calculated for each lesion using a dedicated software (PET VCAR; GE Healthcare), which semiautomatically delineates the tumour's contours with a maximum standardised uptake value (SUVmax) threshold of 42% within the lesion. tMTV was obtained summing each lesion's MTV. Potential prognostic parameters for overall survival (OS) were analysed (tMTV, SUVmax, bone/liver metastasis, neutrophil:lymphocyte ratio ≥4, Eastern Cooperative Oncology Group performance status ≥2, lactate dehydrogenase above the upper limit of normal). RESULTS: Overall, 34 patients treated with first line-pembrolizumab and 40 patients treated with EGFR tyrosine kinase inhibitors were included. In the pembrolizumab group, the median follow-up was 20.3, while the median OS was 4.7 months (95% confidence interval [CI] = 0.3-9.1) for patients with tMTV ≥75 cm3 vs not reached (NR) for patients with tMTV <75 cm3 (95% CI = NR-NR; hazard ratio [HR] = 5.37; 95% CI = 1.72-16.77; p = 0.004). No difference was found in the control group (HR = 1.43; 95% CI = 0.61-3.34; p = 0.411). CONCLUSION: Our data suggest that tMTV ≥75cm3 can be used as a prognostic biomarker of poor outcomes in patients with PD-L1-high advanced NSCLC treated with first-line pembrolizumab. This information could be useful for the selection of patients who may require the addition of chemotherapy to pembrolizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fluordesoxiglucose F18 , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Tomada de Decisão Clínica , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
4.
Clin Lung Cancer ; 22(5): 423-431, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33849808

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are a promising source of biological information in cancer. Data correlating PD-L1 expression in CTCs with patients' response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are still lacking. METHODS: This is a prospective single-center cohort study enrolling patients with advanced NSCLC. CTCs were identified and counted with the CellSearch system. PD-L1 expression on CTCs was assessed with phycoerythrin-conjugated anti-human PD-L1 antibody, clone MIH3 (BioLegend, USA). Primary endpoint was the correlation between the CTCs PD-L1 expression and overall survival (OS). Among secondary objectives, we evaluated the correlation between PD-L1 expression on CTCs and matched tumor tissue and the correlation of CTC number and baseline tumor size (BTS). RESULTS: Thirty-nine patients treated with anti-PD-1/PD-L1 agents as second- or third-line therapy were enrolled. Patients were divided into 3 groups: no CTC detectable (CTCnull, n = 15), PD-L1 positive CTC (CTCpos, n = 13), and PD-L1 negative CTC (CTCneg, n = 11). Median OS in patients with CTCneg was 2.2 months, 95% confidence interval (CI), 0.8-3.6 (reference) versus 3.7 months, 95% CI, 0.1-7.5 (hazard ratio [HR] 0.33; 95% CI, 0.13-0.83; P = .019) in patients with CTCpos versus 16.0 months, 95% CI, 2.2-29.8 (HR 0.17; 95% CI, 0.06-0.45; P< .001) in patients with CTCnull. No correlation was found between PD-L1 expression on CTCs and on tumor tissue. CTC number was correlated with BTS. CONCLUSION: PD-L1 expression on CTCs is a promising biomarker in patients with NSCLC treated with ICIs. Further validation as predictive biomarker is needed.

5.
Lung Cancer ; 145: 95-104, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32417680

RESUMO

OBJECTIVES: ICIs have been approved and are routinely administered regardless of performance status (PS), despite randomized clinical trials of ICIs alone or combined with chemotherapy or target therapy enrolled patients with ECOG PS 0 or 1, while patients with ECOG PS 2 or more were excluded. MATERIALS AND METHODS: We carried out a meta-analysis of available clinical studies exploring the prognostic impact of PS ≥ 2 on Overall Survival (OS), Progression Free Survival (PFS) or Overall Response Rate (ORR) in patients with non small cell lung cancer (NSCLC) treated with immunotherapy (any line). RESULTS: We reviewed 19 studies, comprising 3600 NSCLC patients, 757 of whom with ECOG PS > 1 (average 21.0%, range 6.0-48.6%). In the overall population PS ≥ 2 resulted in worse OS, PFS and ORR (OS pooled hazard ratio of 2.72; 95% CI: 2.03-3.63; I2 72.70%, p < 0.001; PFS pooled hazard ratio of 2.39; 95% CI 1.81-3.15, p < 0.0001; I2 73.03%; ORR pooled odds ratio 0.25; 95% CI 0.11-0.56, p 0.001; I2 0.00%). CONCLUSION: ECOG PS ≥ 2 retains an important prognostic validity in patients treated with ICI similar, in terms of effect size, to that reported for chemotherapy in NSCLC. The high level of heterogeneity for OS and PFS analysis (but not for ORR), not completely explained by the different proportion of ECOG 3-4 patients (ranging from 0% to 50% of the PS ≥ 2 population), could be the result of both patient heterogeneity within the PS 2 population and the subjectivity of ECOG PS assessment. Whether poorer PS is also a predictor of lower immunotherapy efficacy remains still to be demonstrated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...