[Advanced melanoma with low-burden and low-risk disease: a clinical case.].

The management of patients with advanced melanoma is becoming more complex than in past years, due to the recent innovations in the therapeutic scenario. New treatment options, such as the immunotherapeutic combination of ipilimumab and nivolumab, and new BRAF and MEK inhibitors recently introduced, namely encorafenib and binimetinib, were recently approved by the Italian regulatory entities, enriching the systemic therapy armamentarium. In this context, tailoring the therapeutic strategy basing on the patient's characteristics is even more crucial to improve the clinical outcome.

Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients.

Background: The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging.

Objectives: The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination.

Design: We conducted a longitudinal retrospective study examining mRCC patients pre-treated with one or more lines of therapy among different cancer centers in Italy.

Real World Analysis of Peritoneal Metastasis From Renal Cell Carcinoma. Meet-Uro27.

Background: Peritoneal metastases (PM) have been reported in approximately 1% of patients with metastatic Renal Cell Carcinoma (mRCC). Outcome data are limited due to the rarity of this metastatic site. Therefore, the aim of our study is to describe renal cell carcinoma (RCC) patients with PM treated as per clinical practice.

Using peripheral immune-inflammatory blood markers in tumors treated with immune checkpoint inhibitors: An INVIDIa-2 study sub-analysis.

The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of <3.

Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC).

Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases.

Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study.

Background: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs).

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

Background: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC).

Patients And Methods: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration.

Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020.

Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab.

To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. The drug score classified patients into three risk groups with significantly different survivals.

A systematic review and meta-analysis on the optimal treatment duration of checkpoint inhibitoRS in solid tumors: The OTHERS study.

No clear evidence supports the advantage of fixed (up to two years (2yICI)) or continuous treatment (more than two years (prolonged ICI)) in cancer patients achieving stable disease or response on immune checkpoint inhibitors (ICIs). We performed a systematic review and meta-analysis of randomized controlled trials reporting the duration of ICIs (alone or in combination with standard of care (SoC)) across various solid tumors. Overall, we identified 28,417 records through database searching.

Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer.

Purpose: No evidence exists as to whether type 2 diabetes mellitus (T2DM) impairs clinical outcome from immune checkpoint inhibitors (ICI) in patients with solid tumors.

Experimental Design: In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose-lowering medications (GLM) for T2DM had shorter overall survival (OS) and progression-free survival (PFS). We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment (TME) of patients with or without diabetes.

The role of blood cholesterol quality in patients with advanced cancer receiving immune checkpoint inhibitors.

Introduction: Immune checkpoint inhibitors (ICIs) became the standard of care for several solid tumors. A limited fraction of patients (pts) achieves a long-term benefit. Plasmatic and intracellular cholesterol levels have emerged as promising biomarkers.

Immune checkpoint inhibitors in non-conventional histologies of renal-cell carcinoma.

For years, prospective randomized clinical trials excluded patients with non-conventional histologies of renal cell carcinoma (RCC). The paucity of data has led to adopting the same treatment strategies used for clear-cell RCC (ccRCC). In the present narrative review, we explored state of the art about use of immune checkpoint inhibitors (ICIs) in variant histologies of RCC.

Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a).

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20-25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23).

The impact of proton-pump inhibitors administered with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction.

Concomitant Drugs Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Receiving Ipilimumab and Nivolumab in the Compassionate Use Program in Italy: Brief Communication.

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting.

Comparison Between First Line Target Therapy and Immunotherapy in Different Prognostic Categories of BRAF Mutant Metastatic Melanoma Patients: An Italian Melanoma Intergroup Study.

Background: BRAF and MEK inhibitors target therapies (TT) and AntiPD1 immunotherapies (IT) are available first-line treatments for BRAF v600 mutant metastatic melanoma patients. ECOG PS (E), baseline LDH (L), and baseline number of metastatic sites (N) are well-known clinical prognostic markers that identify different prognostic categories of patients. Direct comparison between first-line TT and IT in different prognostic categories could help in first line treatment decision.

The latest developments in biomarkers predicting response to immunotherapy.

Tweetable abstract Biomarkers predicting response to immune checkpoint inhibitors can facilitate the selection of patients who benefit from immunotherapy, avoiding rapid disease progression in nonresponders and needless toxicity.

Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade.

Background: We previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications.

Materials And Methods: We evaluated the prognostic ability of a "drug score" computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival.