Evaluación del perfil de seguridad del medicamento tocilizumab en pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug tocilizumab in patients suspected or confirmed by COVID-19

Introducción: La enfermedad de COVID-19, es una enfermedad emergente cuya patogénesis se relaciona con la tormenta de citocina, la interleucina 6 juega un papel importante en la tormenta de citocinas. El medicamento tocilizumab, es un anticuerpo monoclonal humanizado, el cual se une al receptor soluble IL-6. En pacientes con COVID-19 se ha observado que el uso de tocilizumab disminuye la inflamación exacerbada. Ante este nuevo uso del medicamento es relevante establecer el balance beneficio-riesgo en estos pacientes con COVID-19, identificando con ello las reacciones adversas a medicamentos que pueden estar relacionadas al uso de tocilizumab. Materiales y métodos: Estudio de farmacovigilancia descriptivo y transversal en una cohorte retrospectiva en pacientes sospechosos o confirmados por COVID-19 en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México, México en el periodo 05 de mayo del 2020 al 20 de enero del 2021. Resultados: De los 36 pacientes participantes en este estudio, la edad promedio fue 53 años, de los cuales 30 fueron hombres y 6 fueron mujeres. Las comorbilidades identificadas en este estudio fue la hipertensión arterial sistémica, seguida de la diabetes mellitus tipo II. En la evaluación de los estudios de laboratorio se observó que 2 pacientes desarollaron neutropenia moderada, mientras que en 5 pacientes se identificó trombocitopenia leve y 2 pacientes desarrollaron trombocitopenia moderada. Las infecciones bacterianas identificadas en el estudio con el uso del medicamento fueron: 5 aislamientos de Klebsiella oxytoca, 4 a Escherichia coli y 4 a Pseudomonas aeruginosa... (AU)

Introduction: COVID-19 is a new emerging disease which pathogenesis is mediated by a cytokines storm, interleukin 6 plays an important part of this storm. Tocilizumab is a humanized monoclonal antibody that binds to the IL-6 receptor. In patient with COVID-19, exacerbated inflammation has been observed to decrease when given tocilizumab. Due to the new use of this drug is relevant to stablish the risk-benefit ratio in COVID-19 patients, by identifying the drug adverse reactions that may be related to the use of tocilizumab. Material and methods: Descriptive and cross-sectional pharmacovigilance study in a retrospective cohort in patients suspected or confirmed by COVID-19 in the National Institute of Cardiology in Mexico City, Mexico from May 5, 2020 to January 20, 2021. Outcomes: From 36 patients in this study, the average age was 53 years of which 30 were men and 6 were women. The comorbidities identified in this study were systemic arterial hypertension followed by type II diabetes mellitus. Evaluating the laboratory results we observed 2 patients developed moderate neutropenia, 5 patients presented mild thrombocytopenia and 2 patients moderate thrombocytopenia. The bacterial infections identified in the study with the use of the tocilizumab were: 5 isolates Klebsiella oxytoca, 4 isolates Escherichia coli and 4 Pseudomonas aeruginosa. Conclusion: Knowing the possible drug adverse reactions that occurred in patients with COVID-19 who were administered tocilizumab, allow us to the identify the risks associated with the drug, determining the safety profile and be alert of bacterial infections, neutropenia, and thrombocytopenia, throughout a pharmacotherapeutical follow up, thereby identifying possible associated alterations possibly restated with the use of tocilizumab. (AU)

Safety and efficacy of the patency capsule.

INTRODUCTION AND AIMS: The patency capsule is an effective diagnostic method for preventing video capsule retention in the small bowel during capsule endoscopy. The most frequently associated complication when using the patency capsule is symptomatic retention. The aim of the present study was to evaluate the effectiveness and safety of patency capsules administered to patients at a tertiary care hospital center. MATERIALS AND METHODS: A retrospective observational study was conducted that included all the patients with confirmed Crohn's disease that were administered a patency capsule, within the time frame of January 2019 and December 2020. PC diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value were evaluated, in relation to capsule endoscopy and double-balloon endoscopy findings. Complications associated with the patency capsule were also identified. RESULTS: Thirty patients were included, in whom the patency capsule had 83% sensitivity, 100% specificity, 100% positive predictive value, and 96% negative predictive value, with a diagnostic yield of 96.7%. There was one complication (3.3%) and it resolved spontaneously. CONCLUSIONS: The patency capsule is a safe and effective method for reducing video capsule retention during capsule endoscopy in patients with Crohn's disease.

Corticosteroid safety in COVID-19 patients: a pharmacovigilance study / Seguridad de corticoesteroides en pacientes con COVID-19: un estudio de farmacovigilancia

The use of oral and intravenous corticosteroids as a treatment for SARS-CoV-2 infection has been shown to inhibit the exaggerated inflammatory response, reducing symptoms and days of hospitalization of patients. However, its use is controversial because not enough clinical studies have been made to verify the safety of the drugs. Objective: To assess the safety profile of corticosteroids treatment, at high and low doses, in suspected or confirmed patients with COVID-19, determining the most frequent side effects in patients, and assessing whether the administration of the drugs represents a greater benefit than the risk of presenting these effects. Methods: Ambispective study of active pharmacovigilance at a cohort of confirmed or suspected COVID-19 patients, treated with intravenous and oral corticosteroids. 366 patients were evaluated and divided into 3 groups: use of methylprednisolone (155 mg average) every 24 hours for 3 days, dexamethasone (6 mg) every 24 hours for 10 days, and a control group. Results: The distribution of the cases with hyperglycemia was 33 in high doses and 82 with low doses of corticosteroids and both high and low doses have a similar distribution in cases of infections. When evaluating the harshness and severity of hyperglycemia in the two groups with corticosteroids, it is observed that patients with high doses present more harsh (48%). In case of harshness and severity of infections it is observed that patients with high doses present more harsh (62%) and more severe (79%) cases than those who were administered low doses. (AU)

El uso de corticoides orales e intravenosos como tratamiento para la infección por SARS-CoV-2 ha demostrado inhibir la respuesta inflamatoria exagerada, reduciendo los síntomas y los días de hospitalización de los pacientes. Sin embargo, su uso es controvertido porque no se han realizado suficientes estudios clínicos para verificar la seguridad de los medicamentos. Objetivo: Evaluar el perfil de seguridad del tratamiento con corticoides, a dosis altas y bajas, en pacientes con sospecha o confirmación de COVID-19, determinando los efectos secundarios más frecuentes en los pacientes, y valorando si la administración de los fármacos representa un mayor beneficio que el riesgo de presentar estos efectos. Métodos: Estudio ambispectivo de farmacovigilancia activa en una cohorte de pacientes confirmados o sospechosos de COVID-19, tratados con corticoides intravenosos y orales. Se evaluaron 366 pacientes y se dividieron en 3 grupos: uso de metilprednisolona (155 mg promedio) cada 24 horas por 3 días, dexametasona (6 mg) cada 24 horas por 10 días y un grupo control. Resultados: La distribución de los casos con hiperglucemia fue de 33 casos usando dosis altas y 82 con dosis bajas de corticoides, tanto las dosis altas como las bajas tienen la misma distribución en los casos de infecciones. Al evaluar la severidad y gravedad de la hiperglucemia en los dos grupos con corticoides, se observa que los pacientes con dosis altas presentan mayor gravedad (48%). En caso de severidad y gravedad de las infecciones se observa que los pacientes con dosis altas presentan casos más graves (62%) y más severos (79%) que los que recibieron dosis bajas. (AU)

Which model of small bowel capsule endoscopy has a better diagnostic yield? A systematic review and meta-analysis.

Background and study aims: Small-bowel capsule endoscopy (SBCE) is a safe and efficient method for diagnosis of small-bowel diseases. Since its development, different models have appeared. The aim of this study was to analyze which of the different models of SBCE has the best diagnostic yield. Patients and methods: Extensive medical literature research was reviewed, using MESH terms, searching studies comparing different SBCE types. We analyzed the diagnostic yield of all the comparisons and when there were 2 or more studies that compared the same model of SBCEs, a meta-analysis was performed. Results: Ten eligible studies including 1065 SBCEs procedures were identified. The main indication was occult gastrointestinal bleeding in 9/10 studies. Two of them included anemia, chronic diarrhea and/or chronic abdominal pain. The indication in one article was celiac disease. In 9 studies, different types of SBCEs (MiroCam, Endocapsule, OMOM and CapsoCam) were compared with PillCam (SB, SB2 and SB3). Three studies compared MiroCam vs PillCam and CapsoCam vs PillCam, while two studies contrast Endocapsule vs PillCam. None of the SBCEs show superiority over PillCam [OR 0.78 (95%CI;0.60-1.01)]. One study compared SBCEs other than Pillcam (MiroCam vs Endocapsule). Nine studies did not find statistical differences between SBCEs, one showed better diagnostic yield of Mirocam compared with PillCam SB3 (p=0.02). The difference between these SBCE was not replayed in the metaanalysis [OR 0.77 (95%CI;0.49-1.21)]. Conclusions: Despite the appearance of new SBCE models, there are no differences in diagnostic yield; therefore, SBCE endoscopist's performance should be based on experience and availability.

Evaluación del perfil de seguridad del medicamento lopinavir/ritonavir (Lpv/r) en los pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug lopinavir/ritonavir (Lpv/r) in suspected or confirmed COVID-19 patients

Introducción: El nuevo SARS-CoV-2, es el agente causal de la enfermedad COVID-19. La Organización Mundial de la Salud (OMS) ha referenciado el uso del lopinavir/ritonavir (Lpv/r), es un inhibidor de la proteasa del virus de inmunodeficiencia humana adquirida (VIH-1). El estudio clínico de Cao et al., identificó que el uso de Lpv/r no se asociaron con un mayor número de eventos adversos en comparación con el tratamiento estándar.Materiales y métodos: Estudio retrospectivo de farmacovigilancia en una cohorte en pacientes sospechosos o confirmados de COVID-19 en un hospital de tercer Nivel de la Ciudad de México en el periodo 01 abril 2020 al 30 julio 2020. Resultados: El tratamiento de Lpv/r incluyó 140 pacientes, de los cuales 91 pacientes completaron el tratamiento, mientras que 50 pacientes no terminaron el esquema. Los principales motivos de la suspensión del esquema del medicamento fueron: alta por mejoría (11 casos), defunciones (10 casos) y por inicio de ruxolitinib (9 casos). Además, se identificaron 8 reacciones adversas al medicamento, de las cuales 5 son reacciones asociadas a los trastornos gastrointestinales (diarreas) y las otras 3 reacciones asociadas a trastornos hepatobiliares (hipertransaminasemia).Conclusión: El perfil de seguridad del medicamento Lpv/r demostró una coherencia con las observaciones de estudios previos en relación en los eventos adversos presentados de tipo gastrointestinales y hepáticos, estos últimos se encuentran relacionados a interacción fármaco-fármaco, por lo que sugerimos un seguimiento farmacoterapéutico para identificar las interacciones y las reacciones adversas durante el uso Lpv/r. (AU)

Abstract: The new SARS-CoV-2 is the causal agent for COVID-19. The World Health Organization (WHO) referenced the use of lopinavir/ritonavir (Lpv/r), which is a protease inhibitor of human inmunodeficiency virus (HIV-1). The Clinical trial by Cao et al. identified that the use of Lpv/r has not been associated with any increase of adverse drug reactions within compared to the standard of care.Materials and methods: Pharmacovigilance retrospective study of patients suspected or confirmed with COVID-19 in a 3rd level hospital in Mexico City from April, 01 2020 to July, 30 2020.Results: Lopinavir/ritonavir treatment was prescribed 140 patients from which 91 patients completed the treatment, while 50 patients did not completed the treatment. The cause suspensions were: patient discharge for improvement (11 cases), deaths (10 cases) and start of ruxolitinib (9 cases). In addition, were identify 8 adverse drug reaction from which 5 were associated to gastrointestinal disorders (diarrhea) and 3 hepatobiliary disorders (hypertransaminasemia).Conclusion: The safety profile of the Lpv/r demonstrated consistency with the observations of previous studies in relation to gastrointestinal and hepatic adverse events, which were related to drug-drug interaction, so we suggest a pharmacotherapeutic monitoring to identify them as well as adverse drug reactions due to Lpv/r. (AU)

Neoadjuvant chemotherapy with or without radiotherapy versus upfront surgery for resectable pancreatic adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The role of neoadjuvant chemotherapy (NC) in resectable pancreatic cancer (RPC) has yet to be defined. This review aims to analyze the benefit of NC in RPC compared with upfront surgery (US) in terms of overall survival (OS) and disease-free survival (DFS). PATIENTS AND METHODS: PubMed, CENTRAL (The Cochrane Library), and Embase were systematically reviewed until 3 November 2021. Abstract proceedings and virtual meeting presentations from the American Society of Clinical Oncology and the European Society of Medical Oncology conferences, reference articles of published clinical trials, and review articles were considered. Only randomized clinical trials (RCTs) comparing NC administration with or without radiotherapy previous with surgery (experimental arm) versus US followed by adjuvant chemotherapy with or without radiotherapy (control arm) for RPC were included. RESULTS: A total of 1135 studies were screened. Of these, 1117 studies were primarily excluded. Of the remaining 18 studies, 5 were excluded because of no adequate trial design for this work and 7 others had no available results. Finally, 6 trials with 469 patients with pancreatic cancer randomized to NC (n = 212) or US (n = 257) were selected. Compared with US, NC significantly improved OS [hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.58-0.98; P = 0.033] and DFS (HR 0.73; 95% CI 0.59-0.89; P = 0.002). While the NC approach was not significantly associated with lower resection rate [relative risk (RR) 0.92; 95% CI 0.84-1.01; P = 0.069], the R0 resection rate was significantly higher for NC than for US (RR 1.31; 95% CI 1.13-1.52; P = 0.0004). CONCLUSION: This is the first meta-analysis of RCTs showing that NC improves OS for RPC compared with US followed by adjuvant therapy. Ongoing RCTs should confirm these findings with FOLFIRINOX to generalize the indication of NC.

Can physiological stimulation prior to ileostomy closure reduce postoperative ileus? A prospective multicenter pilot study.

BACKGROUND: The aim of this study was to assess the impact of ileostomy closure following preoperative physiological stimulation (PPS) on postoperative ileus (POI) in patients with loop ileostomy after low anterior resection for rectal cancer. METHODS: Patients who underwent ileostomy closure between January 2017 and February 2020 in two tertiary referral centers were prospectively included. PPS stimulation was compared to standard treatment. Stimulation was carried out daily during the 15 days prior to ileostomy closure by the patient's self-instillation of 200 ml of fecal contents from the ileostomy bag via the efferent loop, using a rectal catheter. Standard treatment (ST) consisted of observation. Outcomes measures were POI, morbidity, stimulation feasibility, and predictors to ileus. RESULTS: A total of 58 patients were included [42 males and 16 females, median age 67 (43-85) years]. PPS was used in 24 patients, who completed the entire stimulation process, and ST in 34 patients. No differences in preoperative factors were found between the two groups. POI was significantly lower in the PPS group (4.2%) vs the ST group (32.4%); p < 0.01, OR: 0.05 (CI 95% 0.01-0.65). The PPS group had a shorter time to restoration of bowel function (1 day vs 3 days) p = 0.02 and a shorter time to tolerance of liquids (1 day vs 2 days), p = 0.04. Age (p = 0.01), open approach at index surgery, p = 0.03, adjuvant capecitabine (p = 0.01). and previous abdominal surgeries (p = 0.02) were associated with POI in the multivariate analysis. C-reactive-protein values on the 3rd (p = 0.02) and 5th (p < 0.01) postoperative day were also associated with POI. CONCLUSIONS: PPS for patients who underwent ileostomy closure after low anterior resection for rectal cancer is feasible and might reduce POI.

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Utility of capsule endoscopy in the diagnosis of gastrointestinal graft-versus-host disease.

INTRODUCTION AND AIM: Graft-versus-host disease (GvHD) is a complication of hematopoietic cell transplantation, and the small bowel is one of the main targets in the gastrointestinal tract. Capsule endoscopy is a safe procedure and can be useful in the diagnosis of GvHD. The aim of the present study was to compare the diagnostic yield of capsule endoscopy with the histopathologic findings in GvHD. MATERIALS AND METHODS: A retrospective diagnostic test study included all the patients with suspected GvHD that underwent gastroscopy and colonoscopy, with histopathologic evaluation of the biopsies taken, and capsule endoscopy, within the time frame of July 2015 and July 2019. Capsule endoscopy findings were compared with the histopathologic diagnosis, considered the gold standard. RESULTS: Twenty-one patients with GvHD (7 [33%] women; 37 ± 11.9 years of age) were included, 20 (95%) of whom had acute GvHD. The median gastric transit time of the capsule was 55 minutes (20-113) and the median small bowel transit time was 261 minutes (238-434). The entire small bowel was visualized through capsule endoscopy in 17 cases (80.95%). The histopathologic findings and capsule endoscopy findings resulted in the diagnosis of GvHD in 17 and 16 cases, respectively. There was agreement between the histopathologic and capsule endoscopy findings in 18 cases (15 positive and 3 negative). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic yield of capsule endoscopy were 88%, 75%, 94%, 60%, and 85%, respectively. CONCLUSIONS: Capsule endoscopy is a safe tool for the diagnosis of GvHD, with high sensitivity and positive predictive value, as well as moderate agreement with histopathologic findings.

SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy.

BACKGROUND: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. PATIENTS AND METHODS: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. RESULTS: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. CONCLUSIONS: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.

Pneumatosis intestinalis in a radioactive iodine-refractory metastasic thyroid papillary carcinoma with BRAFV600E mutation treated with dabrafenib-trametinib: a case report.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors. CASE PRESENTATION: A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAFV600E mutation was treated with dabrafenib and trametinib as a compassionate use. After 4 months treatment, positron emission tomography-computed tomography (PET-CT) showed PI. At the time of diagnosis, the patient was asymptomatic without signs of peritonitis. The initial treatment was conservative and no specific treatment for PI was needed. Unfortunately, after dabrafenib-trametinib withdrawal, the patient developed tumor progression with significant clinical worsening. CONCLUSIONS: This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms.

Recent advances in neoadjuvant immunotherapy for urothelial bladder cancer: What to expect in the near future.

Urothelial bladder cancer (UC) is the most common malignancy involving the urinary system and represents a significant health problem. Immunotherapy has been used for decades for UC with intravesical bacillus Calmette-Guérin (BCG) set as the standard of care for non-muscle-invasive bladder cancer (NMIBC). The advent of immune checkpoint inhibitors (ICIs) has completely transformed the treatment landscape of bladder cancer enabling to expand the treatment strategies. Novel ICIs have successfully shown improved outcomes on metastatic disease to such an extent that the standard of care paradigm has changed leading to the development of different trials with the aim of determining whether ICIs may have a role in early disease. The localized muscle-invasive bladder cancer (MIBC) scenario remains challenging since the recurrence rate continues to be high despite all therapeutic efforts. This article will review the current experience of ICIs in the neoadjuvant setting of UC, the clinical trials landscape and finally, an insight of what to expect in the immediate and mid-term future.

Complete response to immune checkpoint inhibitors-based therapy in advanced renal cell carcinoma patients. A meta-analysis of randomized clinical trials.

BACKGROUND: A major breakthrough with immunotherapy is its potential to achieve complete responses (CR) in a subset of advanced renal cell carcinoma (RCC) patients. We aim at evaluating the incidence and relative risk (RR) of CR in RCC patients treated with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. The proportion of patients with CR events and the derived 95% confidence intervals (CIs) were calculated for each study. Combined relative risks (RRs) and 95% CIs were calculated using fixed- or random-effects methods. The analysis was performed in the intention to treat population, in the PD-L1 expressing (≥1%) RCC tumors and in patients treated with the combination of ICIs and anti-VEGFR tyrosine kinase inhibitors. RESULTS: Six articles were considered for final analysis (total of 4.531 patients). The incidence of CR was 6.2% with ICIs and 2.6% with SOC. Treatment with ICIs significantly increased the risk of achieving CR compared to SOC (RR = 2.40; P = 0.001). This data was confirmed for patients treated with the combination of ICIs plus anti-VEGFR tyrosine kinase inhibitors (RR = 2.50; P = 0.002). In PD-L1 positive tumors, the incidence of CR was 10.0% with ICIs and 4.0% in the SOC arm (RR = 2.49; P < 0.0001). CONCLUSIONS: ICIs provide higher rates of CR compared to SOC, even higher in patients with PD-L1 positive tumors.

Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (CRPC): a post hoc analysis of two randomized clinical trials.

In castration-resistant prostate cancer (CRPC) patients, observational studies have reported that statins may boost the antitumor activity of abiraterone (AA) and data suggest an improvement in efficacy; conclusions with vitamin D are less clear but an eventual benefit has been pointed. We conducted a post hoc analysis of individual patient data of CRPC patients treated with prednisone and/or AA with or without statins/vitamin D on randomized clinical trials. In the COU-AA-301 trial, use of AA with statin and vitamin D reduced the risk of death by 38% (p = 0.0007) while AA alone was associated with a decrease of 10% (p = 0.025), compared to prednisone alone. Meanwhile, in the COU-AA-302 trial, use of AA plus statin plus vitamin D was associated with a reduced risk of death of 26% (p = 0.0054). In this data analysis from two prospective randomized clinical trials, statin and vitamin D use was associated with superior overall survival in metastatic CRPC patients treated with AA and prednisone. To our knowledge, this is the first report suggesting the impact of statin plus vitamin D in this population. New strategies using big data may help to clarify these questions easily and in a most cost-effective approach.

SEOM clinical guideline for treatment of kidney cancer (2019).

In this article, we review de state of the art on the management of renal cell carcinoma (RCC) and provide recommendations on diagnosis and treatment. Recent advances in molecular biology have allowed the subclassification of renal tumours into different histologic variants and may help to identify future prognostic and predictive factors. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. No adjuvant therapy has demonstrated a clear benefit in overall survival. Considering the whole population of patients with advanced disease, the combination of axitinib with either pembrolizumab or avelumab increase response rate and progression-free survival, compared to sunitinib, but a longer overall survival has only been demonstrated so far with the pembrolizumab combo. For patients with IMDC intermediate and poor prognosis, nephrectomy should not be considered mandatory. In this subpopulation, the combination of ipilimumab and nivolumab has also demonstrated a superior response rate and overall survival vs. sunitinib. In patients progressing to one or two antiangiogenic tyrosine-kinase inhibitors, both nivolumab and cabozantinib in monotherapy have shown benefit in overall survival compared to everolimus. Although no clear sequence can be recommended, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in patients with metastatic RCC.