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1.
World J Clin Oncol ; 12(11): 1037-1046, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34909398

RESUMO

BACKGROUND: Non-clear cell (ncc) metastatic renal-cell carcinoma (RCC) has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart. New systemic combination therapies have emerged for metastatic RCC (mRCC), but the pivotal phase III trials excluded patients with nccRCC, which constitute about 30% of metastatic RCC cases. AIM: To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup. METHODS: The present study is a multicenter retrospective observational analysis aiming to assess the activity, efficacy, and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting. RESULTS: Overall, 48 patients were included. At the median follow-up of 40.6 mo, the objective response rate was 27.1%, the disease control rate was 83.3%, and the median progression-free survival and overall survival were 12.3 (95% confidence interval [CI]: 3.6-20.9) and 27.7 (95%CI: 18.2-37.1) mo, respectively. Grade 3 adverse events occurred in 20% of patients, and no grade 4 or 5 toxicities were found. CONCLUSION: Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.

2.
Curr Oncol Rep ; 23(12): 147, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748099

RESUMO

PURPOSE OF REVIEW: Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC. RECENT FINDINGS: The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.

3.
Acta Oncol ; : 1-6, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736367

RESUMO

INTRODUCTION: METEOR was a phase 3 trial (NCT01865747) of cabozantinib versus everolimus in adults with advanced or metastatic clear cell RCC previously treated with VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs). This post hoc analysis of METEOR compared outcomes for patients recruited from European and non-European countries. MATERIAL AND METHODS: Adults with advanced/metastatic clear cell RCC who had received ≥ 1 prior VEGFR-TKI treatment were randomized 1:1 to receive cabozantinib or everolimus. Patients were categorized by recruitment region: Europe or outside of Europe (rest of world [RoW]). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events (AEs) were compared between regional subgroups. RESULTS: In total, there were 320 eligible patients from Europe (cabozantinib, 167; everolimus, 153) and 338 from RoW (North America, 240 patients; Asia-Pacific, 86; Latin America, 12; randomized as cabozantinib, 163; everolimus, 175). PFS and OS were longer with cabozantinib than with everolimus and similar for the Europe and RoW subgroups. For PFS, the hazard ratio (HR) for cabozantinib versus everolimus was 0.54 for the Europe subgroup (p < .001) and 0.50 for the RoW subgroup (p < .001). For OS, the HR was 0.75 for the Europe subgroup (p = .034) and 0.69 for the RoW subgroup (p = .006). ORR in the Europe subgroup was 15% for cabozantinib and 3.9% for everolimus (p < .001). For the RoW subgroup, ORR was 20% for cabozantinib and 2.9% for everolimus (p < .001). Incidence of grade 3/4 AEs were similar for the Europe (cabozantinib, 74%; everolimus, 58%) and RoW subgroups (cabozantinib, 69%; everolimus, 64%). CONCLUSION: In the METEOR trial, efficacy outcomes for patients recruited from European and non-European countries favored cabozantinib over everolimus. The efficacy and safety results for the regional subgroups were consistent with those of the overall METEOR population.

4.
J Thorac Oncol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34648948

RESUMO

INTRODUCTION: In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up. METHODS: Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs). RESULTS: After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65-0.90) and PD-L1 less than 1% (0.64; 0.51-0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population. CONCLUSIONS: At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.

5.
Cancers (Basel) ; 13(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204877

RESUMO

BACKGROUND: Depatuxizumab Mafodotin (Depatux-M; ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. MATERIALS AND METHODS: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety. RESULTS: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0-1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3-10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients; no grade 4 ocular toxicity was reported. No death was considered to be drug-related. CONCLUSIONS: The study reported the first "real world" experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.

6.
N Engl J Med ; 383(13): 1218-1230, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32945632

RESUMO

BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance. METHODS: In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety. RESULTS: Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively. CONCLUSIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Análise de Sobrevida , Neoplasias Urológicas/mortalidade , Urotélio
7.
Clin Genitourin Cancer ; 18(6): 477-488, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32732112

RESUMO

BACKGROUND: Immunotherapy has brought clinical benefits to patients with metastatic renal cell cancer (mRCC). Most patients tolerate immunotherapy but serious immune-related adverse events (irAEs) have been reported. Some studies indicate a correlation between irAEs and clinical response in other cancer types (eg, lung cancer and melanoma). For patients with mRCC, the impact of irAE on clinical outcome is unknown. PATIENTS AND METHODS: A retrospective review of 167 patients with mRCC treated with nivolumab as standard of care between March 2017 and January 2018 in 16 Italian centers was performed. irAEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. The median time to appearance of irAEs was 10 weeks; 38.8% of patients required steroid treatment. The most common irAEs were cutaneous (33.7%) and gastrointestinal (23.3%). The median overall survival and progression-free survival were 20.13 and 7.86 months, respectively. Patients with irAEs showed a greater overall survival (hazard ratio, 0.38; 95% confidence interval [CI], 0.23-0.63) and progression-free survival (hazard ratio, 0.44; 95% CI, 0.29-0.66) benefit as well as better overall response rate (27.3% vs. 13.7%; odds ratio, 2.36; 95% CI, 1.03-5.44) and disease control rate (68.8% vs. 48%; odds ratio, 2.4; 95% CI, 1.23-4.67) if compared with those without irAEs. No correlation was found between steroid use and clinical outcomes. CONCLUSIONS: Our analysis revealed that the appearance of irAEs was associated with better outcomes in patients treated with nivolumab. This data may be limited by sample size and the retrospective nature of the study.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Itália/epidemiologia , Neoplasias Renais/tratamento farmacológico , Nivolumabe/efeitos adversos , Estudos Retrospectivos
8.
Crit Rev Oncol Hematol ; 142: 141-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401421

RESUMO

Knowledge about molecular mechanisms driving development and progression of renal cell carcinoma has been elucidated by different studies. In few years we discovered a large difference between genomic landscapes of clear cell and non-clear cell carcinoma. Moreover, tumor heterogeneity and different acquisition of gene mutations during tumor progression are issues of particular interest. In this review we focalized our attention on principal genomic alterations identified among RCC subtypes. Acquired gene mutations may be an adaptive response to several external pressure including metabolic, treatment, genomic and immune-related external pressure. Thus we correlated and discussed principal genomic alterations adopted by tumor to escape from each external pressures. The aim of the present work is to summarize current knowledge about genomic alterations in RCC with special interest of treatment strategies tailored on the basis of disease mutations assessment.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Mutação , Medicina de Precisão , Animais , Carcinoma de Células Renais/genética , Genômica , Humanos , Neoplasias Renais/genética
9.
Clin Cancer Res ; 25(13): 3839-3846, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30967420

RESUMO

PURPOSE: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy. EXPERIMENTAL DESIGN: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR)

Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Inflamação/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Índice de Massa Corporal , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Inflamação/diagnóstico , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Prognóstico , Índice de Gravidade de Doença , Resultado do Tratamento
10.
BJU Int ; 123(1): 98-105, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29956884

RESUMO

OBJECTIVE: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. PATIENTS AND METHODS: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7-6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. CONCLUSION: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/secundário , Everolimo/uso terapêutico , Feminino , Humanos , Indazóis , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Retratamento , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Taxa de Sobrevida
11.
Am J Clin Oncol ; 42(1): 42-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30204614

RESUMO

OBJECTIVE: The activity of cabozantinib in nonclear cell histologies has not been evaluated. MATERIALS AND METHODS: Data were collected across 24 Italian hospitals. Patients were aged 18 years and older with advanced nonclear cell renal cell carcinoma (RCC), with an Eastern Cooperative Oncology Group Performance Status 0 to 2, who had relapsed after previous systemic treatments for metastatic disease. Cabozantinib was administered orally at 60 mg once a day in 28 days cycles. Dose reductions to 40 or 20 mg were made due to toxicity. Adverse events (AEs) were monitored using CTCAE version 4.0. RESULTS: Seventeen patients were enrolled. Three (18%) patients were diagnosed type I papillary RCC, 9 (53%) type II papillary, 3 (18%) chromophobe, and 2 (11%) with Bellini duct carcinoma. In total, 11 patients started with 60 mg. Six patients started a lower dose of 40 mg. Median progression-free survival was 7.83 months (0.4 to 13.4 mo), while median overall survival was not reached but 1-year overall survival was about 60%. Six patients (35%) experienced a partial response to treatment and 6 patients (35%) showed a stable disease. In the remaining 5 (30%), we observed a progressive disease. Grade 3 and 4 AEs were observed in 41% of patients. Among 20 patients, only 1 (6%) discontinued treatment due to AEs. Asthenia (41%), diarrhea (35%), aminotransferase increasing (35%), mucosal inflammation (35%), hand and foot syndrome (24%), and hypothyroidism (24%) were the most frequently AEs. CONCLUSIONS: Our data showed that, cabozantinib is a active and feasible treatment in patient with nonclear cell RCC.


Assuntos
Anilidas/efeitos adversos , Anilidas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Administração Oral , Idoso , Anilidas/administração & dosagem , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Resultado do Tratamento
13.
Anticancer Res ; 38(8): 4913-4918, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30061269

RESUMO

BACKGROUND/AIM: The specific characteristics of patients who are most likely to benefit from pazopanib therapy are still uncertain. We report on the results of an Italian multicenter, retrospective analysis investigating the factors associated with longer response to first-line pazopanib in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Adult patients were considered if they had received treatment with pazopanib (800 mg/day) for >12 months in the first-line setting. RESULTS: In total, 112 patients were evaluated. Median duration of pazopanib treatment was 22.6 months (IQR 17.8 months). Median PFS was 22.6 months (95%CI= 20.2-25.0). Eighty-three patients (74.1%) had a PFS ≥18 months. Median OS was 32.9 months (95%CI=30.2-35.6). At statistical analysis, only PS score (1+ vs. 0) was significantly associated with PFS (HR=1.76; 95%CI=1.02-3.05; p=0.04). CONCLUSION: Pazopanib therapy may be suitable for all patients with mRCC, and especially in those with PS 0.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Indazóis , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
PLoS One ; 13(7): e0199642, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979712

RESUMO

BACKGROUND: Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care. METHODS: Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ≥1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0. RESULTS: A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported. CONCLUSION: The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Itália , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Retratamento , Análise de Sobrevida , Resultado do Tratamento
16.
Clin Genitourin Cancer ; 16(4): e945-e951, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753637

RESUMO

BACKGROUND: The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment with at least one previous antiangiogenic inhibitor. The aim of this analysis was to evaluate the safety and activity of cabozantinib in an unselected population. METHODS: Data were collected across 24 Italian centers. Cabozantinib therapy was initiated at physician request between September and December 2016. Patients with mRCC with disease that progressed after one or more prior systemic treatment were evaluated. Cabozantinib 60 mg was administered orally once daily. Doses were reduced to 40 mg or 20 mg in patients experiencing grade 3 or intolerable grade 2 adverse events (AEs). RESULTS: Data from 96 patients were evaluated. Cabozantinib was administered as second-line therapy in 28 patients (29%) and as third-line therapy in 18 patients (19%), while the remaining 50 patients (52%) received cabozantinib in further treatment lines. Sixty-six patients began therapy with the full dose of 60 mg. Because of poor performance status, 29 patients began therapy with a reduced dose of 40 mg and 1 patient with 20 mg. At the time of our analysis, grade 3/4 AEs were observed in 35 patients (36%). Only 5 patients discontinued treatment as a result of AEs. Partial response was observed in 35 patients (36%), whereas 33 (34%) had stable disease and 28 (30%) progressive disease. Median progression-free survival was 8.0 months. CONCLUSION: Cabozantinib showed acceptable tolerability and activity in a large unselected population treated according to everyday clinical practice.


Assuntos
Anilidas/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Oncotarget ; 8(33): 55575-55581, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903444

RESUMO

BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response. The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEV. METHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46). Radiologic assessments at first disease assessment (day 46) were used to calculate the relative change in the sum of the products of perpendicular diameters of all measurable lesions determined by either T1 contrast and T2/FLAIR. RESULTS: In patients treated with BEV, the best ETS cut-off was reduction of 15% with T1 contrast and of 40% with T2/FLAIR. Adopting this cut-off for T1 contrast radiological changes, ETS was a significant predictor of OS for patients treated with BEV (HR = 0.511, 95%CI:0.269-0.971, p = 0.040). The cut-off obtained for T2/FLAIR was not significantly correlated with OS (p = 0.102), but we found a trend for correlation with survival when considering the variable as continuous (p = 0.058). CONCLUSIONS: ETS evaluating T1 contrast reduction is a helpful predictor of survival in patients with recurrent GBM treated with BEV, and if validated in a larger prospective trial could be a helpful surrogate endpoint.

18.
Oncotarget ; 7(26): 40085-40094, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27223078

RESUMO

We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies.


Assuntos
Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Docetaxel , Seguimentos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/uso terapêutico
19.
Neuro Oncol ; 18(9): 1304-12, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26951379

RESUMO

BACKGROUND: Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting. METHODS: Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms. RESULTS: Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents. CONCLUSION: Single-agent bevacizumab may have a role in patients with recurrent glioblastoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos de Nitrosoureia/administração & dosagem , Compostos Organofosforados/administração & dosagem , Prognóstico , Taxa de Sobrevida
20.
Future Oncol ; 11(22): 3083-90, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26437324

RESUMO

BACKGROUND: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. PATIENTS & METHODS: All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. RESULTS: Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. CONCLUSIONS: Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. The interest in this strategy may be increased because of the showed efficacy of early DCT chemotherapy in patients with bulky disease (CHAARTED study) and the potential lower efficacy of the new hormonal agents abiraterone acetate and enzalutamide when used in a immediate sequencing.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Progressão da Doença , Docetaxel , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/mortalidade , Retratamento , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
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