Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Per Med ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873959

RESUMO

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.

2.
Expert Rev Anticancer Ther ; : 1-7, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34738499

RESUMO

BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

3.
J Transl Med ; 19(1): 328, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344414

RESUMO

BACKGROUND: Severe immune-related Adverse Events (irAEs) develop in 10-27% of patients treated with Immune-Oncology (IO) [Powles (Lancet 391:748-757, 2018); Galsky (Lancet 395:1547-1557, 2020); Haanen (Ann Oncol 28:119-142, 2017)]. The aim of our study was to evaluate efficacy and clinical outcome of metastatic renal cell carcinoma (mRCC) patients who stopped Immune Checkpoint Inhibitors (ICIs) due to early Grade (G) 3-G4 irAEs. METHODS: We retrospectively collected data from 204 mRCC patients treated with ICIs in 6 Italian referral centers adhering to the Meet-Uro group, between February 2017 and January 2020. To properly weight the results, patients who did not report early G3-G4 toxicities have been included as control group. Primary endpoint was to evaluate 6 months Progression Free Survival (PFS) after early treatment interruption for Grade (G) 3-4 toxicities compared to the control group. Secondary endpoints were to evaluate Time to treatment failure (TTF) and overall survival (OS) in both groups. All statistical analyses were performed using SPSS software (version 19.00, SPSS, Chicago). RESULTS: 18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after only one or two administrations. Immune related nephritis and pancreatitis were the most common irAE that lead to treatment interruption. 6/18 patients received IO-IO combination whereas 12/18 patients antiPD1. In the study group, 12/18 (66.6%) were free from progression at 6 months since IO interruption, TTF was 1.6 months (95% CI 1.6-2.1), mPFS was 7.4 months (95% CI 3.16-11.6) and mOS was 15.5 months (5.1-25.8). In the control group 111/184 (60.3%) patients were free from progression at 6 months, TTF was 4.6 months (95% CI 3.5-5.6), mPFS was 4.6 months (95% CI 3.5-5.6) and mOS was 19.6 months (95% CI 15.1-24.0). In the overall population, mPFS was 5.0 months (95% CI 4.0-5.9) and mOS was 19.6 months (95% CI 15.1-24.0). CONCLUSIONS: ICIs seem to maintain efficacy even after early interruption due to severe irAE.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Itália , Neoplasias Renais/tratamento farmacológico , Estudos Retrospectivos
4.
Cancers (Basel) ; 13(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34359706

RESUMO

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

5.
Cancers (Basel) ; 13(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200770

RESUMO

Collecting duct carcinoma (CDC) is a rare and highly aggressive kidney cancer subtype with poor prognosis and no standard treatments. To date, only a few studies have examined the transcriptomic portrait of CDC. Through integration of multiple datasets, we compared CDC to normal tissue, upper-tract urothelial carcinomas, and other renal cancers, including clear cell, papillary, and chromophobe histologies. Association between CDC gene expression signatures and in vitro drug sensitivity data was evaluated using the Cancer Therapeutic Response Portal, Genomics of Drug Sensitivity in Cancer datasets, and connectivity map. We identified a CDC-specific gene signature that predicted in vitro sensitivity to different targeted agents and was associated to worse outcome in clear cell renal cell carcinoma. We showed that CDC are transcriptionally related to the principal cells of the collecting ducts providing evidence that this tumor originates from this normal kidney cell type. Finally, we proved that CDC is a molecularly heterogeneous disease composed of at least two subtypes distinguished by cell signaling, metabolic and immune-related alterations. Our findings elucidate the molecular features of CDC providing novel biological and clinical insights. The identification of distinct CDC subtypes and their transcriptomic traits provides the rationale for patient stratification and alternative therapeutic approaches.

6.
Tumori ; 107(6): 542-549, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33153416

RESUMO

BACKGROUND: Cabozantinib strongly inhibits osteoclast differentiation and bone resorption in vitro. We aimed to evaluate its effect on bone turnover markers (BTMs) in metastatic renal cell carcinoma. METHODS: This is a monocentric prospective study on patients with mRCC treated with cabozantinib between October 2016 and July 2018. We collected blood samples at baseline and after 3 and 6 months of treatment. We compared sets of data obtained from plasma samples in the whole population with unpaired 2-tailed Student t tests and data for a subset of patients for which all timepoints were available with paired 2-tailed Student t tests. We used the Kaplan-Meier method for survival analyses and the log-rank test to compare the curves. RESULTS: Our analysis included 39 patients. At month 3, the mean C-terminal cross-linked telopeptides of type I collagen (CTx) and the mean N-terminal propeptide of type 1 collagen (PINP) levels were significantly decreased in the whole population (p = 0.013 and p < 0.0001, respectively), as well as at paired analysis (p = 0.015 and p = 0.045, respectively). No differences were observed between baseline and 6 months (p = 0.053 and p = 0.087, respectively). After 3 months, the mean parathyroid hormone (PTH) levels significantly increased in the whole population (p = 0.004), as well as at paired analysis; the mean PTH levels increased significantly at 3 and 6 months, respectively (p = 0.019 and p = 0.041, respectively). Changes in BTM levels were not associated with outcome. CONCLUSIONS: Cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx and showed a transient secondary increase of PTH.

7.
Ther Adv Med Oncol ; 12: 1758835920970081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335565

RESUMO

Background: Neoadjuvant anthracycline-taxane-based chemotherapy (ChT) is a standard of care treatment option for stage II-III breast cancer (BC) patients. However, the optimal duration of neoadjuvant ChT has been poorly investigated so far. Material and methods: We retrospectively retrieved clinical data of patients with stage II-III human epidermal growth factor receptor 2-negative (HER2-) BC who were treated between October 2007 and January 2018 with neoadjuvant AT (doxorubicin-paclitaxel) for three cycles followed by CMF (cyclophosphamide-methotrexate-5-fluorouracil) for three cycles (cohort A) or with four AT cycles followed by four CMF cycles (cohort B). The aim of our study was to investigate the impact of neoadjuvant ChT duration (cohort A versus cohort B) on pathological complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS). Results: Of 209 HER2- BC patients included, 62 had triple-negative breast cancer (TNBC) and 147 had hormone receptor-positive (HR+) BC. Median age was 48 years (range 30-74 years). A total of 111 patients belonged to cohort A and 98 patients belonged to cohort B. pCR was detected in 29 (13.9%) patients, 25 (40.3%) of whom had TNBC and four (2.7%) had HR+ HER2- BC. Patients achieving pCR had significantly longer DFS and OS, with statistical significance reached only in patients with TNBC. We found no differences between cohort A and cohort B in terms of pCR rates (15.3% versus 12.2%; p = 0.55), DFS (p = 0.49) or OS (p = 0.94). The incidence of grade 3/4 adverse events was similar in cohort A versus cohort B as well (22.5% versus 19.4%; p = 0.54). Conclusion: Shorter duration of neoadjuvant anthracycline-taxane ChT was not associated with worse clinical outcomes in patients with stage II-III BC. Prospective studies are needed to evaluate whether the duration of neoadjuvant anthracycline-taxane-based ChT can be reduced in specific patient subgroups without negatively affecting clinical outcomes.

8.
Immunotargets Ther ; 9: 273-288, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224904

RESUMO

Over the last 20 years, different therapies have been considered as the mainstay for the treatment of patients with metastatic renal cell carcinoma (mRCC). Since angiogenesis is a key mechanism in the pathogenesis of renal carcinoma, research is still focusing on the inhibition of new vessel growth through the development of novel and potent tyrosine kinase inhibitors (TKIs), such as cabozantinib. On the other hand, a new therapeutic scenario has opened up in the forefront with immunotherapy. Immune checkpoint inhibitors (ICIs), which already represent a standard treatment option in pretreated mRCC patients, are revolutionizing the frontline therapeutic armamentarium of mRCC. Upfront combination immunotherapy as well as combinations of immunotherapy with targeted agents showed to significantly improved outcomes of mRCC patients compared to single-agent TKIs. ICIs are associated with long-lasting responses. Nonetheless, several unmet needs remain, as a small proportion of patients shows primary refractoriness to immunotherapy. Multiple treatment strategies combining different mechanisms of action or targeting immune escape pathways are emerging with the aim to improve response rates and survival outcomes. This review summarizes current immunotherapeutic targets and therapies approved for mRCC, while examining mechanisms of resistance and future directions, with the aim to address novel treatment strategies and help in improving the management of this tumor.

9.
Am J Clin Oncol ; 43(9): 621-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889831

RESUMO

OBJECTIVES: Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib. MATERIALS AND METHODS: mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared. RESULTS: Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017). CONCLUSION: Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/secundário , Quimiocina CXCL12/sangue , Progressão da Doença , Selectina E/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Indazóis , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/sangue
10.
Front Oncol ; 10: 1644, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903369

RESUMO

Introduction: In the last decades, the therapeutic decision-making approach to metastatic renal cell cancer (mRCC) has dramatically changed thanks to the introduction in the treatment scenario of, first, anti-angiogenic agents and, afterward, immune-checkpoint inhibitors (ICIs). Immunotherapy is now the standard of care in pretreated mRCC patients and has recently entered even the first line setting. Nevertheless, in mRCC as well as in other tumor settings, a durable and clinically meaningful benefit from treatment with ICIs is not obtained for all patients treated. Therefore, the necessity to identify and validate predictive biomarkers of response to immunotherapy has emerged, in order to design the optimal treatment strategy for mRCC patients. Discussion: In this review, we present and discuss the most promising predictive biomarkers of response to ICIs in mRCC with the recent data available. In details, the first marker that was investigated is the immunohistochemical expression of programmed death receptor ligand 1 (PD-L1), showing a negative prognostic role in mRCC, but the debate about its potential predictive value is still open. Additionally, the high heterogeneity in PD-L1 determination methods adds complexity to this issue. Second, the tumor mutational or neoantigen burden is an emerging biomarker of increased response to immunotherapy, hypothesizing that the higher the TMB, the higher is the production of neoantigens, and thus the stimulation of anti-tumor immune response, even though controversial results have been obtained. Third, the tumor microenvironment, namely the different populations of the immune infiltrate, plays a key role in tumor progression and in the response to immunotherapy. Finally, several studies have collected evidence on the potential association of the occurrence of immune-related adverse events (irAEs) with the benefit from ICIs, first in non-small cell lung cancer (NSCLC) and melanoma, and recently even in mRCC. Conclusion: Several promising biomarkers of response to immunotherapy with ICIs have been identified, though without conclusive results upon their potential predictive value in mRCC. Therefore, the results of the exploratory analyses of the recently presented first-line trials and hopefully of future prospective, biomarker-driven studies could provide useful tools to be applied in the everyday clinical practice.

11.
Expert Rev Anticancer Ther ; 20(8): 715-726, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32758032

RESUMO

INTRODUCTION: In prostate cancer , there has recently been an emerging interest in mutations in genes belonging to the homologous recombination repair (HRR) pathway and in the inhibition of poly (ADP-ribose) polymerase (PARP) proteins. AREAS COVERED: Mutations in the HRR genes, including BRCA1, BRCA2, and Ataxia-Telangiesctasia mutated (ATM), have been reported in prostate cancer, with different incidence in the localized and advanced settings. The PARP enzyme complex is involved in repair of DNA damage and its inhibition causes the accumulation of DNA mutations in HRR deficient cells. Several PARP inhibitors (PARPi) are under development, such as olaparib, talazoparib, niraparib, rucaparib, and veliparib. In metastatic castration resistant prostate cancer (mCRPC), olaparib has been the most studied and its clinical efficacy has been validated in a phase III clinical trial. Rucaparib and niraparib have also shown promising results in the preliminary analyzes of two phase II trials, while talazoparib is currently under development. EXPERT OPINION: PARPi have become part of the treatment of mCRPC. Early results of combination therapy with PARPi and new hormonal therapy are promising and are supported by a strong biological rationale. Current results need to be validated in randomized phase III-controlled trials in order to translate the use of PARPi into real world practice.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Reparo do DNA/genética , Desenvolvimento de Medicamentos , Humanos , Masculino , Mutação , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia
13.
Target Oncol ; 15(4): 495-501, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32671807

RESUMO

BACKGROUND: Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy. OBJECTIVE: To describe the outcome of cabozantinib in patients previously treated with immunotherapy. PATIENTS AND METHODS: Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity. RESULTS: Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up. CONCLUSIONS: Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.


Assuntos
Anilidas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/uso terapêutico , Idoso , Anilidas/farmacologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Piridinas/farmacologia , Receptores Proteína Tirosina Quinases/farmacologia
14.
Cancer Treat Rev ; 88: 102057, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32574991

RESUMO

Despite advances in metastatic prostate cancer therapy, expected survival for patients in the castration-resistant phase of disease is poor. Immune-checkpoints inhibitors significantly prolonged life expectancy in some solid tumors and have been evaluated also in advanced stage prostate cancer. The majority of data available derive from preliminary phase I and II trials evaluating CTLA-4 and PD-1 as monotherapy or in combination with each other, vaccines, radiotherapy or targeted/hormonal therapy, achieving only limited benefits in terms of biochemical and radiologic responses. There are many reasons that may explain why prostate cancer responds poorly to modern immunotherapies, such as its characteristic low tumor mutational burden or immune-suppressive tumor microenvironment. The present review summarizes the results obtained treating advanced prostate cancer patients with immune-checkpoints inhibitors and analyzes potential mechanisms of both resistance and sensitivity, in order to hypothesize possible avenues of special interest for future research.


Assuntos
Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/terapia , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Vacinas Anticâncer/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Masculino , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Clin Med ; 9(6)2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32580478

RESUMO

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.

16.
J Clin Med ; 9(4)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231117

RESUMO

The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells' (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.

17.
Tumori ; 106(5): 406-412, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32116138

RESUMO

INTRODUCTION: Therapeutic decision-making in metastatic castration-resistant prostate cancer (mCRPC) represents an open challenge. Radium-223 is approved for patients with symptomatic bone metastases, no visceral involvement, progressing after at least 2 lines of systemic therapy, or ineligible for any other systemic treatment. METHODS: We performed a retrospective, observational study on patients with mCRPC treated with radium-223 at our institution outside of clinical trials, to assess the safety and activity in a real-world population. Data regarding baseline patient/disease characteristics and treatment outcomes (number of cycles, treatment-related adverse events [AEs], cause of discontinuation, and best response) were collected. RESULTS: Overall, 41 patients were treated from September 2015 to September 2018. Median age was 73 years; baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0, 1, or 2 in 15%, 80%, and 5% of cases, respectively; and 3%, 41%, 44%, and 12% of patients had <6, 6-20, >20, and superscan bone lesions, respectively. A median number of 5 cycles (interquartile range 3-6) with median dose 19.52 MBq (interquartile range 12.87-24.83) was received. Treatment schedule was completed in 49% of cases; discontinuations due to AEs, disease-related death, or disease progression occurred in 24%, 33%, and 43% of patients, respectively. Any-grade AEs occurred in 73% and grade 3/4 treatment-related AEs occurred in 29% of patients, mainly anemia, decreased platelet count, and fatigue. No skeletal-related events or treatment-related deaths were recorded. After treatment, 66%, 2%, and 32% of patients had a stable, improved, or deteriorated ECOG PS versus baseline, respectively, and 24%, 61%, and 15% reported a stable, improved, or worsened pain symptom control. Post-treatment versus baseline alkaline phosphatase was reduced or stable in 46% and increased in 54% of patients, whereas prostate-specific antigen was decreased or stable in 83% and increased in 17% of patients. CONCLUSIONS: Our study provides clinically useful real-world data on radium-223, highlighting the importance of multidisciplinary patient management to guarantee the best continuum of care for patients with mCRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/efeitos adversos , Rádio (Elemento)/efeitos adversos , Resultado do Tratamento
18.
Cancers (Basel) ; 12(3)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155941

RESUMO

Background: Single-agent capecitabine (C) is a moderately effective chemotherapeutic compound in the treatment of patients with HER2-negative metastatic breast cancer (mBC). The capecitabine-vinorelbine (CV) combination is also used due to a good tolerability profile, but no studies have demonstrated its superiority over single-agent C. Methods: We conducted a retrospective analysis to compare overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and incidence of adverse events (AEs) in patients with HER2-negative mBC treated with CV vs. single-agent C. Results: Out of 290 patients included in this study, 127 (43.8%) received single-agent C, while 163 (56.2%) patients were treated with CV. Median PFS was similar in patients treated with single-agent C or CV, while CV was associated with significantly longer OS in patients with hormone receptor-positive (HR+) BC. This OS advantage was confirmed at multivariable analysis also after propensity score-based matching of patients according to relevant clinical or tumor characteristics. When compared with single-agent C, CV was associated with higher incidence of G3/G4 and any-grade nausea/vomiting, diarrhea and increased transaminases. Conclusions: While prospective studies are needed to confirm our findings, the potential OS advantage of CV over single-agent C in HR+ mBC patients must be weighed against a significantly higher incidence of AEs.

19.
Immunotherapy ; 12(2): 151-159, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32089035

RESUMO

Aim: INVIDIa was a retrospective, multicenter study, exploring the clinical efficacy of influenza vaccine in 300 cancer patients undergoing immunotherapy. Overall survival (OS) was immature at the initial report. Methods: We reported the final OS analysis from the original study population and within subgroups. Results: Both at the univariate and multivariate analysis, the occurrence of influenza syndrome (IS) was significantly related to better OS in the overall population (OR: 0.53 [95% CI: 0.32-0.88]; p = 0.01). In the lung cancer subgroup, receiving flu vaccine and/or developing IS was related to better OS (p = 0.04). Within elderly patients, the flu vaccine was the main variable for the relative OS advantage (p = 0.05). Conclusion: Receiving the flu vaccine and/or developing IS was related to better OS within the INVIDIa population.


Assuntos
Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/complicações , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Idoso , Feminino , Seguimentos , Humanos , Fatores Imunológicos/imunologia , Influenza Humana/imunologia , Itália , Masculino , Neoplasias/imunologia , Estudos Retrospectivos , Análise de Sobrevida , Síndrome
20.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098246

RESUMO

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Neoplasias Renais , Células Neoplásicas Circulantes , Análise de Célula Única , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...