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PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

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OBJECTIVE: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments. METHODS: A three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon. In the absence of head-to-head comparisons between NIVO + IPI and PEM + AXI, clinical data for NIVO + IPI was obtained from CheckMate 214 (NCT02231749) and for PEM + AXI from KEYNOTE-426 (NCT02853331). A matching-adjusted indirect comparison was conducted to account for the imbalance of treatment effect modifiers between the trials. Patient characteristics, resource use, health state utilities, and costs were based on Brazilian-specific sources. Costs and health outcomes were both discounted by 5% annually in line with Brazilian guidelines. The robustness of the results was evaluated through extensive sensitivity analysis and scenario analyses. RESULTS: When comparing the matched versus unmatched OS, PFS, and TTD curves there was no noteworthy difference. NIVO + IPI was associated with cost savings (R$ 350,232), higher LYs (5.54 vs. 4.61), and QALYs (4.74 vs. 3.76) versus PEM + AXI, resulting in NIVO + IPI dominating PEM + AXI. Key model drivers were the treatment duration for PEM, NIVO, and AXI. NIVO + IPI remained dominant in all scenario analyses, which indicated that model results were robust to alternative modelling inputs or assumptions. CONCLUSIONS: This analysis shows that NIVO + IPI is estimated to be a life-extending and potentially cost-saving 1 L treatment option when compared with PEM + AXI for intermediate/poor-risk a RCC patients in the Brazilian private healthcare system.

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Renal cancer is the seventh most common cancer in men and the tenth in women. The aim of this article is to review the diagnosis, treatment, and follow-up of renal carcinoma accompanied by recommendations with new evidence and treatment algorithms. A new pathologic classification of RCC by the World Health Organization (WHO) was published in 2022 and this classification would be considered a "bridge" to a future molecular classification. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. Adjuvant treatment with pembrolizumab is an option for intermediate-or high-risk cases, as well as patients after complete resection of metastatic disease. More data are needed in the future, including positive overall survival data. Clinical prognostic classification, preferably IMDC, should be used for treatment decision making in mRCC. Cytoreductive nephrectomy should not be deemed mandatory in individuals with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Metastasectomy can be contemplated in selected subjects with a limited number of metastases or long metachronous disease-free interval. For the population of patients with metastatic ccRCC as a whole, the combination of pembrolizumab-axitinib, nivolumab-cabozantinib, or pembrolizumab-lenvatinib can be considered as the first option based on the benefit obtained in OS versus sunitinib. In cases that have an intermediate IMDC and poor prognosis, the combination of ipilimumab and nivolumab has demonstrated superior OS compared to sunitinib. As for individuals with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab and cabozantinib are the options of choice. When there is progression following initial immunotherapy-based treatment, we recommend treatment with an antiangiogenic tyrosine-kinase inhibitor. While no clear sequence can be advocated, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in the setting of metastatic RC.

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Immune checkpoints inhibitors have shown a remarkable improvement in overall survival of stage IV renal cell carcinoma patients. Nevertheless, there is a wide range of immune-related adverse events (IRAE) that arise from these revolutionary treatments. Autoimmune encephalitis is a rare but severe central nervous system IRAE in these cancer patients. The severities of these IRAEs preclude patients from continuing immunotherapy treatment. Few cases of autoimmune encephalitis with immunotherapy have been described in the literature and optimal clinical management of these events as well as patient's immune-mediated response after treatment suspension is still unclear. Here, we report a case of a 67 years-old woman with stage IV renal cell carcinoma under treatment with nivolumab who developed autoimmune encephalitis. After high doses of corticosteroids patient's condition improved significantly with full recovery after 5 days of treatment. Even though nivolumab was not reinstalled, a persistent response of her oncologic disease was evidenced. We expect that this case can contribute to the existing literature of both subjects, the management of autoimmune encephalitis as grade IV immune related adverse event and the responses of immune checkpoint inhibitors after IRAE.

Los inhibidores de puntos de control inmunológico han mostrado una importante mejoría en la supervivencia global de los pacientes con carcinoma de riñón estadio IV. Sin embargo, existe una amplia variedad de efectos adversos inmunomediados que surgen a partir de estos tratamientos revolucionarios. La encefalitis autoinmune es un infrecuente pero grave efecto adverso inmunomediado del sistema nervioso central en estos pacientes. La gravedad de este cuadro impide que los pacientes continúen con el tratamiento de inmunoterapia. Se han descrito pocos casos de encefalitis autoinmune con inmunoterapia en la literatura y aún no está claro el manejo clínico óptimo de estos eventos, ni cómo continua la respuesta inmunomediada después de la suspensión del tratamiento. Presentamos el caso de una mujer de 67 años con carcinoma de células renales estadio IV que desarrolló encefalitis autoinmune durante el tratamiento con nivolumab. La paciente mejoró significativamente luego del inicio del tratamiento con altas dosis de corticoides, con una recuperación completa después de 5 días del mismo. Si bien el nivolumab no se reinició, se evidenció una respuesta persistente de su enfermedad oncológica. Esperamos que este caso pueda contribuir a la literatura existente de ambos temas, el manejo de la encefalitis autoinmune como efecto adverso inmunomediado grado IV y las respuestas que se obtienen con la inmunoterapia luego de estos efectos adversos.

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Surgery has historically been the mainstay of treatment for metastatic renal cell carcinoma (mRCC), but recent clinical trials demonstrated that contemporary systemic therapies alone are non-inferior to cytoreductive nephrectomy (CN). Thus, the current role of surgery is not precisely defined. CN remains an appropriate upfront treatment for the palliation of severe symptoms, select cases of metastatic non-clear cell renal cell carcinoma, for consolidation following systemic therapy, and in the setting of oligometastatic disease. Metastasectomy is ideally utilized to achieve a disease-free state when there is minimal morbidity associated with surgery. Given the heterogenous nature of mRCC, the decision for systemic therapy and surgery should be made through a multidisciplinary approach tailored to each individual patient.

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PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

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BACKGROUND: There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC. METHODS: This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics. RESULTS: A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity. CONCLUSION: There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients' cancer journey.

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As a tumor photodiagnostic agent, 5-aminolevulinic acid (ALA) is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with fluorescence. ALA-PpIX fluorescence was evaluated in human renal cell carcinoma (RCC) cell lines and non-tumor HK-2 cell lines. We found that extracellular PpIX level was correlated with ABCG2 activity, illustrating its importance as a PpIX efflux transporter. Extracellular PpIX was also related to the Km of ferrochelatase (FECH) that chelates PpIX with ferrous iron to form heme. The Vmax of FECH was higher in all RCC cell lines tested than in the HK-2 cell line. TCGA dataset analysis indicates a positive correlation between FECH expression and RCC patient survival. These findings suggest FECH as an important biomarker in RCC. Effects of iron chelator deferoxamine (DFO) on the enhancement of PpIX fluorescence were assessed. DFO increased intracellular PpIX in both tumor and non-tumor cells, resulting in no gain in tumor/non-tumor fluorescence ratios. DFO appeared to increase ALA-PpIX more at 1-h than at 4-h treatment. There was an inverse correlation between ALA-PpIX fluorescence and the enhancement effect of DFO. These results suggest that enhancement of ALA-PpIX by DFO may be limited by the availability of ferrous iron in mitochondria following ALA administration.

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BACKGROUND: Preserving health-related quality of life (HRQOL) is an important goal during renal cell carcinoma treatment. We report HRQOL outcomes from a phase II trial (NCT03173560). PATIENTS AND METHODS: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of 2 different starting doses of lenvatinib (18 mg vs. 14 mg daily) in combination with everolimus (5 mg daily), following one prior vascular endothelial growth factor-targeted treatment. HRQOL was measured using 3 different instruments-FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L-which were all secondary endpoints. Change from baseline was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale. TTD for each treatment arm was estimated using the Kaplan-Meier method. RESULTS: Baseline characteristics of the 343 participants randomly assigned to 18 mg lenvatinib (n = 171) and 14 mg lenvatinib (n = 172) were well balanced. Least-squares mean estimates for change from baseline were favorable for the 18 mg group over the 14 mg group for the FKSI-DRS and most EORTC QLQ-C30 scales, but differences between treatments did not exceed the minimally important thresholds. Median TTD was longer among participants in the 18 mg group than those in the 14 mg group for most scales. CONCLUSIONS: Participants who received an 18 mg lenvatinib starting dose had favorable HRQOL scores and longer TTD on most scales compared with those who received a 14 mg starting dose.

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INTRODUCTION: Dual immunotherapy (ipilimumab/nivolumab, IO/IO) and immunotherapy/tyrosine kinase inhibitor (IO/TKI) combinations (e.g. pembrolizumab/axitinib) are approved for the first-line treatment of intermediate/poor risk metastatic renal cell carcinoma (RCC), but there is limited comparative data between these two options. We sought to understand how oncologists decide between IO/IO vs. IO/TKI. METHODS: We sent a 10-question electronic survey centered on a patient scenario of intermediate/poor risk metastatic RCC to 294 academic/disease-focused and general oncologists in the US. RESULTS: We received 105 responses (36% response rate): 61% (64) of providers chose IO/IO, 39% (41) chose IO/TKI. 78% (82) of oncologists were academic or disease-focused, 22% (23) were general. Academic/disease-focused oncologists were significantly more likely to choose IO/IO (56/82, 68%) than general oncologists (8/23, 35%), P = .004. Among those who chose IO/IO, the perceived main issue with IO/TKI was: long-term toxicities - 31% (20), short-term toxicities - 28% (18), less effective - 28% (18), less convenient - 8% (5). Among those who chose IO/TKI, the perceived main issue with IO/IO was: short-term toxicities - 43% (17), less effective - 28% (11), long-term toxicities - 15% (6), and risk of death - 10% (4). 88% (92) of providers would be comfortable enrolling patients into a phase III trial comparing IO/IO vs. IO/TKI. We found no associations between therapy chosen by a provider and participation as PI in a trial of IO/IO or IO/TKI, or receipt of outside funding from an IO/IO or IO/TKI company. CONCLUSION: In response to a patient scenario of intermediate/poor risk metastatic RCC, 61% of providers chose IO/IO, 39% chose IO/TKI. There was a significant association between type of practice and choice of therapy, with academic/disease-focused oncologists more likely to choose IO/IO. The majority of oncologists would be comfortable enrolling patients into a phase III trial comparing IO/IO vs. IO/TKI.

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PURPOSE: International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes. METHODS: All patients with unilateral Wilms tumor (WT), age > 6 months, treated with preoperative chemotherapy as per protocol, and registered between 2001 and 2011 were eligible. Countries were grouped to give comparable case numbers and geographical representation. Cox univariable and multivariable (MVA) statistics were applied, with the German collaborative group (Gesellschaft für Pädiatrische Onkologie und Hämatologie-Austria, Germany, and Switzerland) as reference for hazard ratios for event-free survival (EFS) and overall survival (OS). RESULTS: A total of 3,176 eligible patients were registered from 24 countries assigned into six groups. Age and histologic risk group distribution were similar across all groupings. The distribution of WT stage varied by country grouping, with 14.9% (range, 11.1%-18.2%) metastatic at diagnosis. Median follow-up was 78.9 months. For localized WT, 5-year EFS varied from 80% (Brazilian group) to 91% (French group; P < .0001), retaining significance only for Brazil in MVA (P = .001). Five-year OS varied from 89% (Brazilian group) to 98% (French group; P < .0001). In MVA, only superior OS in France was significant (P = .001). Five-year EFS/OS for stage IV did not vary significantly. High-risk histology and tumor volume at surgery were significantly associated with increased risk of death in MVA for metastatic disease. CONCLUSION: International benchmarking of survival rates from WT within a large trial/study database has demonstrated statistically significant differences. Clinical interpretation should take account of variation in tumor stage but also treatment factors.

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INTRODUCTION: Immunotherapy revolutionized cancer care in the last decade and, notably among its tools, the programmed cell death protein-1 (PD-1) inhibitors. These drugs are related to increased life expectancy rates. However, they can cause several adverse events that have not been fully characterized, thus challenging clinical practice. OBJECTIVE: To evaluate the toxicity profile, determining its frequency, causality, and severity associated with treatment with PD-1 inhibitors in patients treated at an oncology service in the private health sector in Belo Horizonte. METHODS: Observational, retrospective, and cross-sectional study, based on the review of electronic medical records. The eligibility criteria included patients over 18 years old with a diagnosis of any cancer and staging, receiving a PD-1 inhibitor from January 2017 to January 2020. RESULTS: The sample consisted of 134 patients with lung cancer (46,3%), melanoma (34,3%), and kidney cancer (19,4%). The most common adverse event (AE) related to treatment were fatigue (51.5%), anorexia (23.1%), hypothyroidism (15.7%), and skin rash (14.9%), being grades 1 and 2 more prevalent. Between 3 and 12 months, there were more cutaneous, nutritional, and metabolic toxicities, and fatigue was present throughout the entire treatment period. Gastrointestinal and pulmonary toxicities were more frequent up to the 9th month. CONCLUSION: Based on real-world evidence, it was possible to reveal important findings to support the safe practice of PD-1 inhibitors treatment. Fatigue was the most prevalent AE among patients. In addition, the kinetics of AE allowed the identification of major occurrences according to the period o treatment, allowing more precise monitoring and surveillance.

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PURPOSE: Translocation renal cell carcinoma (tRCC) is a subtype that occurs predominantly in children and young individuals. Metastatic tRCC occurring in young patients is more aggressive than that occurring in older patients, and there are still no effective therapies. Organoids can mimic original tissues and be assessed by high-throughput screening (HTS). We aimed to utilize patient-derived organoids and HTS to screen drugs that can be repurposed for metastatic tRCC with PRCC-TFE3 fusion. METHODS: Tumor tissues were obtained from treatment-naïve metastatic tRCC patients who underwent surgery. Histopathology and fluorescence in situ hybridization (FISH) confirmed the tRCC. Organoids derived from the dissected tissues were cultured and verified by FISH and RNA-seq. HTS was performed to seek promising drugs, and potential mechanisms were explored by RNA-seq and cell-based studies. RESULTS: We successfully established a metastatic tRCC organoid with PRCC-TFE3 fusion, a common fusion subtype, and its characteristics were verified by histopathology, FISH, and RNA-seq. An HTS assay was developed, and the robustness was confirmed. A compound library of 1816 drugs was screened. Eventually, axitinib, crizotinib, and JQ-1 were selected for further validation and were found to induce cell cycle arrest and apoptosis. RNA-seq analyses of posttreatment organoids indicated that crizotinib induced significant changes in autophagy-related genes, consistent with the potential pathogenesis of tRCC. CONCLUSIONS: We established and validated organoids derived from tissues dissected from a patient with metastatic tRCC with PRCC-TFE3 fusion and achieved the HTS process for the first time. Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion. Such organoid and HTS assays may represent a promising model system in translational research assisting in the development of clinical strategies.

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Este documento é uma versão resumida do relatório técnico da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec e foi elaborado numa linguagem simples, de fácil compreensão, para estimular a participação da sociedade no processo de Avaliação de Tecnologias em Saúde (ATS) que antecede a incorporação, exclusão ou alteração de medicamentos, produtos e procedimentos utilizados no SUS. As recomendações da Comissão são submetidas à consulta pública pelo prazo de 20 dias. Após analisar as contribuições recebidas na consulta pública, a Conitec emite a recomendação final, que pode ser a favor ou contra a incorporação, exclusão ou alteração da tecnologia analisada. A recomendação final é, então, encaminhada ao Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde -SCTIE/MS, que decide sobre quais tecnologias em saúde serão disponibilizadas no SUS

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INTRODUÇÃO: Os carcinomas de células renais representam 2-3% de todos os cânceres, com maior incidência em países ocidentais, são o sétimo mais comum em homens e o nono mais comum em mulheres e vêm apresentando uma tendência de aumento em sua prevalência. De acordo com os dados do GLOBOCAN (Agência Internacional de Pesquisa sobre o Câncer) de 2018, número estimado de novos casos de CCR no Brasil foi de 10.688 com uma taxa geral padronizada por idade (ASR) de 4,3 por 100.000 habitantes e um número de mortes estimadas em 2018 de 4.084. A nefrectomia radical é o tratamento de escolha para os doentes com câncer renal e as taxas de cura podem ser muito altas para tumores de estádio 1 (>90%). O sunitinibe e pazopanibe foram recomendados pela Conitec para tratamento de CCR. Assim, o objetivo deste relatório é avaliar a eficácia e segurança, bem como custo-efetividade e impacto orçamentário das associações ipilimumabe/nivolumabe e pembrolizumabe/axitinibe visando a incorporação como primeira linha de tratamento de pacientes adultos com CCRm. TECNOLOGIA: Ipilimumabe (Yervoy ®), nivolumabe(Opdivo®), pembrolizumabe (Keytruda®) e axitinibe (Inlyta®). PERGUNTA: As associações ipilimumabe/nivolumabe ou pembrolizumabe/axitinibe são eficazes, seguras e cust

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INTRODUÇÃO: Os carcinomas de células renais representam 2-3% de todos os cânceres, com maior incidência em países ocidentais, são o sétimo mais comum em homens e o nono mais comum em mulheres e vêm apresentando uma tendência de aumento em sua prevalência. De acordo com os dados do GLOBOCAN (Agência Internacional de Pesquisa sobre o Câncer) de 2018, número estimado de novos casos de CCR no Brasil foi de 10.688 com uma taxa geral padronizada por idade (ASR) de 4,3 por 100.000 habitantes e um número de mortes estimadas em 2018 de 4.084. A nefrectomia radical é o tratamento de escolha para os doentes com câncer renal e as taxas de cura podem ser muito altas para tumores de estádio 1 (>90%). O sunitinibe e pazopanibe foram recomendados pela Conitec para tratamento de CCR. Assim, o objetivo deste relatório é avaliar a eficácia e segurança, bem como custo-efetividade e impacto orçamentário das associações ipilimumabe/nivolumabe e pembrolizumabe/axitinibe visando a incorporação como primeira linha de tratamento de pacientes adultos com CCRm. TECNOLOGIA: Ipilimumabe (Yervoy ®), nivolumabe(Opdivo®), pembrolizumabe (Keytruda®) e axitinibe (Inlyta®). PERGUNTA: As associações ipilimumabe/nivolumabe ou pembrolizumabe/axitinibe são eficazes, seguras e cust

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In the last decade, the development of immune checkpoint inhibitors have revolutionized the treatment of patients with advanced renal cell carcinoma, with the potential for dramatic changes in the therapeutic landscape. Nivolumab, a monoclonal antibody inhibitor of transmem-brane programmed cell death protein 1 (PD-1), was approved as monotherapy in 2015 for advanced renal cell carcinoma in patients previously treated with an agent targeting vascular endothelial growth factor. In April 2018, the combination of nivolumab and ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 inhibitor, was approved for patients with previously untreated intermediate- and poor-risk advanced renal cell carcinoma. Then, in 2019, combination therapies consisting of pembrolizumab (anti-PD-1) or avelumab (anti-PD-1 ligand, PD-L1) with axitinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) were also approved for use in all risk groups. This review pre-sents a brief historical review of the association between immunology and oncology; describes essential aspects of the mechanism of action of immune checkpoint inhibitors; discusses the current evidence regarding the clinical use of different immunotherapy regimens for the treatment of patients with renal cell carcinoma, both clear cell and other histological types; and provides general information on their adverse effects. The role of appropriate patient selection is analyzed to allow individualization of therapy and improve the already promising results. Finally, per-spectives on the future use of immune checkpoint inhibitors to treat renal cancer are discussed.

En la última década, el desarrollo de inhibidores de puntos de control o checkpoints inmunológicos, ha revolucionado el tratamiento de los pacientes con carcinoma de células renales avanzado avizorándose posibles cambios dramáticos en el escenario terapéutico. Nivolumab, un anticuerpo monoclonal inhibidor de la proteína transmembrana de muerte celular programada 1 (PD-1), se aprobó como monoterapia en 2015 para carcinoma de células renales avanzado en pacientes previamente tratados con algún agente dirigido al factor de crecimiento endotelial vascular. En abril de 2018, la combinación de nivolumab e ipilimumab, un inhibidor del CTLA-4, fue aprobado para pacientes con carcinoma de células renales avanzado de riesgo intermedio y riesgo desfavorable, previamente no tratados. Luego, en 2019, terapias combinadas que consisten en pembrolizumab (anti-PD-1) o avelumab (anti-ligando-PD-1, PD-L1) con axitinib (un inhibidor del receptor tirosina kinasa del factor de crecimiento endotelial vascular); también fueron aprobadas para su uso en todos los grupos de riesgo. En esta revisión se presenta una breve reseña histórica sobre la asociación entre la inmunología y la oncología; se describen aspectos básicos del mecanismo de acción de los inhibidores de puntos de control inmunológicos; se discute la evidencia actual relacionada con el uso clínico de los distintos esquemas de inmu-noterapia para el tratamiento de pacientes con carcinoma de células renales, tanto de células claras como de otros tipos histológicos; y se entrega información general sobre sus efectos adversos. Se analiza el rol de la adecuada selección de pacientes que permita una individualización de la terapia y, por ende, una mejora de los ya promisorios resultados. Por último, se discuten las perspectivas sobre el uso futuro de los inhibidores de puntos de control inmunológicos para el tratamiento del cáncer renal.

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