Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors

Introduction Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy. Material and methods All patients with mRCC treated with first-line TKI, and adequate follow-up, in University Hospital La Paz (Madrid, Spain) between 2007 and 2020 were analyzed. Patients treated inside a clinical trial were excluded from this analysis. Results A total of 90 patients treated with first-line TKI were included. Regarding IMDC criteria, 33 patients (36.7%) were good-risk, 41 patients (45.5%) intermediate-risk, and 16 patients (17.8%) poor-risk. With a median follow-up of 49 months, the median overall survival (OS) for good, intermediate, and poor-risk patients was 54, 24, and 16 months (p = 0.004). When intermediate-risk was divided into patients with 1 or 2 risk factors, differences in OS were also statistically significant: patients with 1 risk factor had a median OS of 33 months, while patients with 2 risk factors had a median OS of 16 months, the same as poor-risk patients (p = 0.003). In the multivariate analysis, trying to find out which of the IMDC factors had a more remarkable weight in the prognosis of the patients, both ECOG and hemoglobin levels by themselves were significantly associated with OS. Conclusion In our group of patients, survival outcomes were different among patients with intermediate-risk with 1 or 2 risk factors by IMDC criteria(AU)

Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors.

INTRODUCTION: Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy. MATERIAL AND METHODS: All patients with mRCC treated with first-line TKI, and adequate follow-up, in University Hospital La Paz (Madrid, Spain) between 2007 and 2020 were analyzed. Patients treated inside a clinical trial were excluded from this analysis. RESULTS: A total of 90 patients treated with first-line TKI were included. Regarding IMDC criteria, 33 patients (36.7%) were good-risk, 41 patients (45.5%) intermediate-risk, and 16 patients (17.8%) poor-risk. With a median follow-up of 49 months, the median overall survival (OS) for good, intermediate, and poor-risk patients was 54, 24, and 16 months (p = 0.004). When intermediate-risk was divided into patients with 1 or 2 risk factors, differences in OS were also statistically significant: patients with 1 risk factor had a median OS of 33 months, while patients with 2 risk factors had a median OS of 16 months, the same as poor-risk patients (p = 0.003). In the multivariate analysis, trying to find out which of the IMDC factors had a more remarkable weight in the prognosis of the patients, both ECOG and hemoglobin levels by themselves were significantly associated with OS. CONCLUSION: In our group of patients, survival outcomes were different among patients with intermediate-risk with 1 or 2 risk factors by IMDC criteria. These could help select patients that may benefit from first-line treatment with a TKI, particularly in settings with difficult access to novel therapies, such as immunotherapy-based combinations.

Proteomics Characterization of Clear Cell Renal Cell Carcinoma.

PURPOSE: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. MATERIAL AND METHODS: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. RESULTS: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. CONCLUSIONS: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

Comparison of 2-Weekly and 3-Weekly Dosing of Docetaxel in Metastatic Prostate Cancer.

INTRODUCTION: Docetaxel 75 mg/m2 every 3 weeks is the standard schedule for metastatic prostate cancer (mPC). Alternative dosing of 50 mg/m2 every 2 weeks may be an option for frail patients. Our aim is to define which factors influence the choice of schedule and to compare the outcomes of both schedules in daily clinical practice. PATIENTS AND METHODS: We retrospectively included patients with mPC treated with docetaxel in our institution. We compared data from patients treated with 3-weekly, 75 mg/m2 docetaxel or 2-weekly, 50 mg/m2 docetaxel, including basal characteristics, predefined prognostic factors, treatment received, toxicity and survival data. RESULTS: We included 200 patients, 86% of whom presented castration resistant mPC. A total of 158 patients (79%) were treated with 3-weekly scheme. Compared with these patients, patients treated with 2-weekly scheme were significantly older, had higher Eastern Cooperative Oncology Group performance status (ECOG PS) and Charlson Comorbidity Index, presented more visceral metastases and needed opioid treatment more frequently. Patients treated with 2-weekly scheme presented shorter median overall survival; however, these differences were not shown after multivariate analysis with significant prognostic factors. Patients treated with 2-weekly scheme had more treatment delays and suspensions, but less clinically impairing toxicities such as febrile neutropenia, neuropathy and diarrhea; toxic deaths were 5 in the 3-weekly group while none in the 2-weekly group. CONCLUSION: Compared to docetaxel 75 mg/m2 every 3 weeks, dosing of 50 mg/m2 every 2 weeks may be an alternative for older, frailer and more comorbid patients. Two-weekly dosing may be used more frequently in selected patients.

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction.

Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity:  two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.

A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis.

BACKGROUND: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. METHODS: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. RESULTS: Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01). CONCLUSIONS: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.