•The use of immune-check point inhibitors in urothelial cancers is gaining momentum.•Pharmacokinetic and pharmacodynamic may offer more answers for patients and drug selection.•Anti-PD-1-PD-L1 have ...manageable toxicity profile.•Chemotherapy plus pembrolizumab showed promising results in terms of ORR.•Additional biomarkers need to be developed for patient selection for anti-PD-1/PD-L1.
Chemotherapy is the reference treatment for patients with advanced urothelial carcinoma, both in the neo-adjuvant and adjuvant settings; however, the overall outcome remains poor in this patient population. In the last few years, the addition of immune checkpoint inhibitors into the therapeutic armamentarium has changed the therapeutic landscape of several tumor types, including urothelial carcinoma. Many different molecules have been introduced in the clinical use and several questions about immunotherapies are currently open and deserve a critical analysis. The current review article is aimed at describing the clinical pharmacology of monoclonal antibodies targeting PD-1 axis in urothelial malignancies to underline pharmacodynamic and pharmacokinetic differences among them.
•The use of immune-check point inhibitors in urothelial cancers is gaining momentum.•Pharmacokinetic and pharmacodynamic may offer more answers for patients and drug selection.•Pembrolizumab showed ...higher incidence of adverse events vs all other moAbs.•Chemotherapy plus pembrolizumab showed promising results in terms of ORR.•Additional biomarkers need to be developed for patient selection for anti-PD-1/PD-L1.
Chemotherapy is the reference treatment for patients with advanced urothelial carcinoma, both in the neo-adjuvant and adjuvant settings; however, the overall outcome remains poor in this patient population. In the last few years, the addition of immune checkpoint inhibitors into the therapeutic armamentarium has changed the therapeutic landscape of several tumor types, including urothelial carcinoma. Many different molecules have been introduced on the market and several questions about immunotherapies are currently open and deserve a critical analysis. The current review article is aimed at describing the clinical pharmacology of monoclonal antibodies targeting PD-1 axis in urothelial malignancies to underline possible pharmacodynamic and pharmacokinetic differences among them.
Purpose
To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (
eNOS
) and interleukin-8 (
IL
-
8
) genes and risk of developing ...bevacizumab-related adverse events in metastatic breast cancer (mBC) patients.
Patients and methods
mBC patients candidate to receive bevacizumab-based chemotherapy were enrolled in this pharmacogenetic study.
eNOS
c.-813C>T and c.894G>T, and
IL
-
8
c.-251A>T were analyzed by real time PCR on genomic DNA extracted from peripheral blood. Univariate analysis was performed to test the association between each SNP and treatment-related toxicities.
Results
Seventy-six mBC patients were enrolled in the present study. Patients carrying the homozygous variant
eNOS
c.-813TT genotype showed a statistically significant occurrence of any grade proteinuria when compared to CT or CC genotypes (
p
= 0.004). No significant association of proteinuria with
IL-8
SNP or hypertension with selected
eNOS
and
IL-8
SNPs was found.
Conclusions
These findings suggest an association between the
eNOS
c.-813C>T polymorphism and the development of proteinuria in mBC patients receiving a bevacizumab-based chemotherapy.
Circulating tumor DNA, circulating tumor cells and tumor-related exosomes may offer new opportunities to provide insights into the biological and clinical characteristics of a neoplastic disease. ...They represent alternative routes for diagnostic and prognostic purposes, and for predicting and longitudinally monitoring response to treatment and disease progression. Hence, circulating biomarkers represent promising noninvasive tools in the scenario of pancreatic cancer, where neither molecular nor clinical predictors of treatment benefit have been identified yet. This review aims to provide an overview of the current status of circulating biomarker research in pancreatic cancer, and discusses their potential clinical utility to facilitate clinical decision-making.
•Castration resistant prostate cancer depends on aberrant androgen signaling.•Hormonal treatment has revolutionized the management of the disease.•The sequence of therapies should be based on stage ...and molecular changes.•Treatment can be optimized on the basis of the molecular profile of the tumor.
Tumor heterogeneity strongly affects the molecular mechanisms driving resistance to hormonal therapies in castration-resistant prostate cancer. Since the current use of available treatments can be optimized on the basis of the molecular profile of tumor, the present review focuses on genetic biomarkers in prostate cancer and their application to a personalized treatment.
Abstract only
e14054
Background: Immunotherapy has revolutionized the treatment of NSCLC. However, response rate is variable, with a substantial failure rate. Thus, the identification of predictive ...biomarkers of response to immunotherapy is an area of great interest. Methods: Patients with locally advanced or metastatic NSCLC treated with nivolumab or pembrolizumab were enrolled. Disease response was defined following RECIST criteria (v. 1.1). Four ml of plasma were collected for the analysis of exosomal mRNA levels of PD-L1 (e-PD-L1) and IFN-γ (e-IFN-γ) at baseline and at the time of first radiological assessment. Exosome isolation and mRNA extraction was obtained by the exoRNeasy kit (Qiagen, Valencia, CA). e-PD-L1 and e-IFN-γ were evaluated by the QX100 ddPCR (Bio-Rad, Hercules, CA) and expressed as allele frequency (%). Chest computed tomography (CT) scan at baseline was used for the radiomic analysis. Tumor segmentation was performed on DICOM-formed images taken from the picture archiving, and the regions of interest were delineated manually and analyzed using the QUIBIM SL software. Survival was calculated stratifying patients based on e-PD-L1 and e-IFN-γ median values. Results: Nivolumab was given to 17 patients as 2nd line and to 8 subjects as further line of treatment, while 13 patients received 1st line pembrolizumab. Median PFS was 11 vs 16.2 months (mos) in patients with baseline e-PD-L1 of < 0.3% vs ≥0.3%, respectively (p = 0.16). e-PD-L1 significantly increased in disease progression (PD) vs partial response (PR) and disease stabilization (SD) (p = 0.01) after 2 mos of treatment. In patients with e-IFN-γ ≥4.1% vs < 4.1% at baseline, median PFS was 5.6 mos vs not reached, respectively (p = 0.003). The multiparametric radiomic analysis identified the Cluster Prominence Value (CPV, p = 0.012) and the Cluster Shade Value (CSV, p = 0.034) as significantly correlated with treatment outcome. Moreover, the D2d parameter and e-IFN-γ were inversely correlated (p < 0,0001). CPV and D2d reflect the intra-tumor architecture, including necrosis, cell proliferation, and angiogenesis. Conclusions: Liquid biopsy data correlate with radiomic parameters and predict response to immunotherapy.
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