Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Ther Adv Chronic Dis ; 13: 20406223211063023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35070248

RESUMO

Lurbinectedin is responsible for DNA recognition and binding, producing double-strand DNA (dsDNA) breaks thus resulting in apoptosis. Sensitivity to lurbinectedin is linked to the nucleotide excision repair (NER) system. Furthermore, irinotecan, a topoisomerase I inhibitor, provokes dsDNA breaks that could be reinforced abrogating the NER system using lurbinectedin. BRCA-mutated patients, already treated with platinum-derived drugs, who suffered DNA damage, cannot repair the breaks due to lurbinectedin interaction, whereas irinotecan provokes a dsDNA break that promotes synthetic lethality. This article describes an exceptional response to lurbinectedin alone followed by the association with irinotecan in a BRCA-mutated platinum-resistant ovarian cancer patient. A 44-year-old BRCA1-mutated ovarian cancer patient was treated in sixth line with lurbinectedin and irinotecan with a time to further progression (TTFP) equal to 8 months. In our case, the association with irinotecan overcame the resistance to lurbinectedin alone. In conclusion, lurbinectedin and irinotecan demonstrated a promising response in platinum-resistant patients. However, further studies should be conducted to validate our findings and future trials will be important to further define the clinical utility of lurbinectedin.

2.
J Clin Pathol ; 75(1): 39-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33144356

RESUMO

AIMS: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1). METHODS: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed. RESULTS: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC. CONCLUSION: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.


Assuntos
Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores/metabolismo , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Análise Serial de Tecidos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
3.
J Oncol Pharm Pract ; 28(3): 750-753, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34964671

RESUMO

INTRODUCTION: Immunotherapy dramatically changed history of melanoma patients with a clinical benefit never seen before. Nevertheless, severe and unexpected adverse effects can occur, fortunately rarely. CASE PRESENTATION: We reported the case of a 75-year-old male patient affected by metastatic melanoma who developed myocarditis and acute rhabdomyolysis with secondary diaphragmatic dysfunction and consequent pulmonary restrictive syndrome after Nivolumab monotherapy. Blood tests and ultrasonography of the diaphragm revealing left hypokinesis suggested a Nivolumab-related rhabdomyolysis, as an immune-mediated adverse event. The rhabdomylolysis involved the diaphragm with consequent diaphragmatic weakness and respiratory distress. MANGEMENT & OUTCOME: The patient had a slow but slight and progressive improvement of symptoms and vital signs post-treatment with high-dose corticosteroids. DISCUSSION: With this case report, we want to highlight the importance of rapid recognition and treatment of rare and unexpected, but potential serious immune-related adverse events. These events might happen despite the remarkable clinical benefits of immune checkpoint inhibitors. We do not know which patients will benefit from these therapies and why, when and in which cases adverse event will occur: we must not lower our attention.


Assuntos
Melanoma , Miocardite , Segunda Neoplasia Primária , Insuficiência Respiratória , Rabdomiólise , Idoso , Diafragma , Humanos , Masculino , Melanoma/tratamento farmacológico , Miocardite/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Nivolumabe/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Rabdomiólise/induzido quimicamente
4.
Thorac Cancer ; 13(3): 483-488, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34939342

RESUMO

BACKGROUND: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (mNSCLC) and ECOG performance status (PS) of 2 treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. METHODS: To explore the role of immune-inflammatory surrogates by the validated lung immuno-oncology prognostic score (LIPS) score, including the neutrophil-to-lymphocyte ratio (NLR) and the pretreatment use of steroids, alongside other prognostic variables. A retrospective analysis of 128 patients with PS2 and PD-L1 ≥50% mNSCLC treated between April 2018 and September 2019 with first-line pembrolizumab in a real-world setting was performed. RESULTS: With a median follow-up of 15.3 months, the 1-year overall survival (OS) and median progression-free survival (PFS) were 32.3% (95% CI: 30.9-33.9) and 3.3 months (95% CI: 1.8-4.7), respectively. The NLR, lactate dehydrogenase (LDH) and pretreatment steroids results were the only significant prognostic factors on the univariate analysis and independent prognostic factors by the multivariate analysis on both OS and PFS. The LIPS score, including the NLR and pretreatment steroids, identified 29 (23%) favourable-risk patients, with 0 factors, 1-year OS of 67.6% and median PFS of 8.2 months; 57 (45%) intermediate-risk patients, with 1 factor, 1-year OS 32.1% and median PFS 2.7 months; 42 (33%) poor-risk patients, with both factors, 1-year OS of 10.7% and median PFS of 1.2 months. CONCLUSIONS: The assessment of pre-existing imbalance of the host immune response by combined blood and clinical immune-inflammatory markers may represent a way to unravel the heterogeneous outcome and assessment of patients with mNSCLC and poor PS in the immune-oncology setting.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Prognóstico , Estudos Retrospectivos
5.
Cancer Manag Res ; 13: 7747-7757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675670

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is an anatomically and biologically distinct entity with a rising incidence and a poor prognosis on conventional treatments. Surgery followed by adjuvant chemotherapy is a potentially curative option in resectable cases, while palliative-intent chemotherapy is the standard-of-care in the advanced setting. Technological advances through massive parallel sequencing have enabled a deeper understanding of disease biology with the identification of several druggable molecular vulnerabilities in nearly 50% of cases. Among them, gene fusions involving the fibroblast growth factor receptor 2 (FGFR2) are the most therapeutically exploited so far with a number of Phase II clinical trials investigating FGFR2 inhibitors showing unprecedented efficacy results in this molecular subgroup. Over the last year, these efforts have culminated in the US FDA-approval of pemigatinib and infigratinib, the first two oral selective FGFR2 targeted agents for previously treated, locally advanced or metastatic iCCA driven by FGFR2 fusion or rearrangements. While first-line Phase III trials are currently underway to test these targeted approach against standard-of-care chemotherapy, translational studies are trying to better understand primary and secondary resistance mechanisms in order to optimize FGFR2 blockade in iCCA. In this article, we extensively reviewed the current evidence on the biological rationale, as well as preclinical and clinical development of FGFR inhibitors in iCCA.

6.
Ther Adv Urol ; 13: 17562872211054302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707691

RESUMO

BACKGROUND: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. OBJECTIVE: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. DESIGN SETTING AND PARTICIPANTS: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. RESULTS AND LIMITATION: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. CONCLUSION: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.

7.
Tumori ; 107(6): NP131-NP135, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34696653

RESUMO

INTRODUCTION: Xp11.2 translocation is a rare subtype of renal cell carcinoma (RCC), identified as a single entity only from 2004 by World Health Organization (WHO). These tumors involve pediatric age group and rarely patients over 40 years old. Children show indolent disease; adult population has invasive tumor at diagnosis with rapid progression. CASE REPORT: We describe a case report of a young woman affected by metastatic clear cell renal carcinoma with Xp11.2 translocation. She achieved a longer stable disease (SD) to first line treatment with atezolizumab plus bevacizumab, obtaining a progression free survival (PFS) of 21 months. After she received cabozantinib, sunitinib and then sorafenib. CONCLUSIONS: The patient had an overall survival (OS) of 51 months, which is much higher than that reported in literature data. Unfortunately, the biology of Xp11.2 translocation RCC and its therapeutic management are still unclear.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/etiologia , Cromossomos Humanos X , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Translocação Genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Carcinoma de Células Renais/terapia , Terapia Combinada/métodos , Feminino , Humanos , Neoplasias Renais/terapia , Metástase Neoplásica , Estadiamento de Neoplasias , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Immunotherapy ; 13(18): 1501-1519, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34670403

RESUMO

Background: Immunotherapy changed the landscape of non-small-cell lung cancer (NSCLC). Efforts were made to implement its action. This study aims to describe body composition, nutritional and inflammatory status in NSCLC patients treated by first-line immunotherapy, their correlation, variation and impact. Patients and methods: We retrospectively analyzed 44 consecutive patients who received pembrolizumab treatment. Results: During the therapy, inflammation and visceral fat increased, whereas muscle and subcutaneous fat decreased. Parameters related to inflammation had an interesting prognostic impact. High numbers of white blood cells remained significantly correlated with a high risk of death in multivariate model. Conclusion: For the best treatment choice, a combination of clinical and biological factors will be most likely be necessary. Prospective and larger studies with a multidimensional approach are needed.


Lay abstract Inflammation and malnutrition in cancer patients may affect the immune system and response to therapy. We noticed an increase in inflammation and visceral fat and a decrease in muscle and subcutaneous fat during therapy. No variation showed a significant correlation with survival. Muscle mass, adipose tissue and body mass index do not confirm any prognostic impact or relationship with response to therapy. More interesting results were observed with parameters related to inflammation. Probably, for the best treatment choice, a combination of clinical and biological factors will be necessary. Further studies with a multidimensional approach are needed to propose the best treatment and the best support to everyone.


Assuntos
Composição Corporal , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Humanos , Inflamação/etiologia , Inflamação/imunologia , Inflamação/terapia , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Tumori ; 107(6): NP123-NP126, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34423700

RESUMO

Immune-related myasthenia gravis is a rare, disabling, and potentially fatal adverse event of immune checkpoint inhibitor treatment. It is important to identify and manage it promptly. We present two cases of immune-related de novo myasthenia gravis observed at the Modena Cancer Center in two elderly patients treated with two anti-PD-1 monoclonal antibodies: cemiplimab and nivolumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Miastenia Gravis/diagnóstico , Miastenia Gravis/etiologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletromiografia , Humanos , Masculino , Miastenia Gravis/terapia , Nivolumabe/administração & dosagem , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Avaliação de Sintomas
10.
Expert Rev Anticancer Ther ; 21(11): 1183-1192, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34424125

RESUMO

INTRODUCTION: In the last decade, there have been substantial changes in the management of metastatic renal cell carcinoma (mRCC) with combined regimens with immune checkpoint inhibitors (ICI) replacing targeted therapies. These combined regimens include the combination of cabozantinib plus nivolumab. AREAS COVERED: Here, we provide an overview of clinical trials evaluating the combination of cabozantinib and nivolumab and the current clinical data on mechanism of action, pharmacokinetics, efficacy, and safety profile. EXPERT OPINION: Dual immune checkpoint inhibition with nivolumab and ipilimumab as well as the combination of a vascular endothelial growth factor (VEGF) inhibitor and an immune checkpoint inhibitor have shown to improve outcomes in phase III trials in comparison to sunitinib (axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, cabozantinib plus nivolumab, lenvatinib plus pembrolizumab). However, to date, there are no head-to-head trials comparing these new combination therapies and no biomarkers are available to guide the optimal choice of first line therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Anilidas , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Piridinas , Fator A de Crescimento do Endotélio Vascular
11.
Clin Nutr ESPEN ; 43: 64-75, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024567

RESUMO

BACKGROUND AND AIMS: Body composition and balance of nutritional and inflammatory status are important for the immune system. Alterations of these aspects may impact on response, outcome and toxicities of immunotherapy. In this review we try to clarify some definitions and tools used for the assessment of the different aspects of nutritional disorders, body composition and inflammatory status with a focus on lung cancer. METHODS: We primary investigate the definitions of malnutrition, cachexia, sarcopenia and overweight. Secondary, tools used to measure body composition, nutritional and inflammatory status, mainly in lung cancer are reviewed. RESULTS: All these features, in the time of precision medicine may improve assessment and selection of patients, incorporating also early palliative care in standard therapy. CONCLUSIONS: A multimodal approach based on nutrition assessment and physical exercise should be evaluated to improve aspects of the immune response against cancer and to propose the best treatment to every patient.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Composição Corporal , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia , Estado Nutricional
12.
J Immunother Cancer ; 9(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34016723

RESUMO

BACKGROUND: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs). METHODS: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety. RESULTS: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2). CONCLUSION: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Neoplasias/tratamento farmacológico , Vacinação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Incidência , Vacinas contra Influenza/efeitos adversos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/imunologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vacinação/efeitos adversos , Adulto Jovem
13.
Ther Adv Med Oncol ; 13: 17588359211019642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046089

RESUMO

BACKGROUND: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. METHODS: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. RESULTS: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. CONCLUSION: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

14.
Eur J Cancer ; 148: 24-35, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33721704

RESUMO

BACKGROUND: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. METHODS: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy. RESULTS: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6-38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5-17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients' features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148). CONCLUSIONS: In the real-world scenario NSCLC patients with PD-L1 expression ≥50% treated with first-line single-agent pembrolizumab achieve worse outcomes as compared to the Keynote-024 trial. Poor post-progression outcomes are major determinants of the global results that should be considered when counselling patients for first-line treatment choices.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Thorac Cancer ; 12(6): 880-889, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33527756

RESUMO

BACKGROUND: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. METHODS: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. RESULTS: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15-1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02-1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52-1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45-1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case-control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17-2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84-2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49-0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45-0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. CONCLUSIONS: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Fumar/tendências , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Análise de Sobrevida
16.
Tumori ; 107(6): NP33-NP36, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33526000

RESUMO

Renal cell carcinoma accounts for 3% of all tumors. Over the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has improved owing to the approval of several drugs such as tyrosine kinase inhibitors and immunotherapy. The median progression-free survival (PFS) does not exceed 8 months with the available drugs in pretreated patients with mRCC. We present a case of a patient with a long-term response to fourth-line treatment with cabozantinib. Our patient obtained a PFS of 33 months, which is much higher than that reported in literature.


Assuntos
Anilidas/uso terapêutico , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Piridinas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Taxa de Sobrevida
17.
Artigo em Inglês | MEDLINE | ID: mdl-33431707

RESUMO

SUMMARY: We present the case of a 69-year-old woman who attended the Endocrinology Unit of Modena for a suspicious lymph node in the left cervical compartment discovered during the follow-up of a recurrent gynecological malignancy. At neck ultrasonography, a thyroid goiter was detected, and the further cytological examination was inconclusive for thyroid nodule and compatible with a localization of an adenocarcinoma with papillary architecture for the lymph node. The histological examination after a left neck dissection confirmed the presence of an intracapsular metastasis of a papillary carcinoma immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8 and negative for thyroglobulin. Subsequently, in the suspicion of a thyroid primitiveness, a total thyroidectomy was performed, revealing an intraparenchymal follicular variant of papillary thyroid carcinoma of 2 mm in the right lobe. During the follow-up, the appearance of a suspected cervical metastatic lesion led to another neck dissection, histologically compatible with a papillary carcinoma localization, immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8, and negative for thyroglobulin. The histological revision of surgical specimens suggests the cervical recurrence of the prior gynecological cancer, rather than a thyroid carcinoma metastasis. The case described shows how carefully the cytological, histological and immunoistochemical results must be evaluated in oncological management, considering the whole patient's history. LEARNING POINTS: Neck lymph node metastases occasionally originate from anatomically distant primary sites, such as breast, lung, gastro-intestinal tract, genito-urinary tract and CNS. Histological and immunohistochemical evaluations play an important role to identify the primary malignant site, although in some cases they could mislead the clinicians. A multidisciplinary approach and the evaluation of the whole medical history of the patient are mandatory to guide the diagnostic-therapeutic path and to avoid unnecessary treatments.

18.
J Med Case Rep ; 14(1): 239, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33287897

RESUMO

BACKGROUND: Mismatch-repair-deficiency resulting in microsatellite instability (MSI) may confer increased radiosensitivity in locally advanced/metastatic tumors and thus radiotherapy (RT) potentially might have a changing role in treating this subset of patients, alone or in combination with checkpoint inhibitors. CASE PRESENTATION: We report a 76 year-old Italian male patient presenting with locally advanced undifferentiated prostate cancer (LAPC), infiltrating bladder and rectum. Molecular analysis revealed high-MSI with an altered expression of MSH2 and MSH6 at immunohistochemistry. Two months after 6 chemotherapy cycles with Docetaxel associated to an LHRH analogue, a computed tomography scan showed stable disease. After palliative RT (30 Gy/10 fractions) directed to the tumor mass with a 3D-conformal setup, a follow-up computed tomography scan at 8 weeks revealed an impressive response that remained stable at computed tomography after 9 months, with sustained biochemical response. To our knowledge, this is the first case of such a sustained response to low dose RT alone in high-MSI LAPC. CONCLUSIONS: Routine evaluation of MSI in patients with locally problematic advanced tumors might change treatment strategy and treatment aim in this setting, from a purely palliative approach to a quasi-curative paradigm.


Assuntos
Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Neoplasias da Próstata , Idoso , Reparo de Erro de Pareamento de DNA , Humanos , Masculino , Instabilidade de Microssatélites , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia
19.
Cancers (Basel) ; 12(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182517

RESUMO

Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of biliary tract cancers from an "orphan" to a "target-rich" disease. Recently, mutations in isocitrate dehydrogenase genes (IDH1/2) and fusions of the fibroblast growth factor receptor have emerged as the most amenable to molecularly targeted inhibition, with several compounds actively investigated in advanced-phase clinical trials. Specifically, the IDH1 inhibitor ivosidenib has been the first targeted agent to show a survival benefit in a randomized phase III trial of cholangiocarcinoma patients harboring IDH1 mutations. In this review article, we will focus on the IDH1/IDH2 pathway, discussing the preclinical rationale of its targeting as well as the promises and challenges of the clinical development of IDH inhibitors in biliary tract cancers.

20.
Ther Adv Med Oncol ; 12: 1758835920968463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224275

RESUMO

BACKGROUND: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. PATIENTS AND METHODS: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. RESULTS: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33). CONCLUSION: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...