A] strong positive beta-3-tubulin expression versus absence cores B) 2+ beta-3-tubulin expression.

<p>A] strong positive beta-3-tubulin expression versus absence cores B) 2+ beta-3-tubulin expression.</p

Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to the combination of c-Myc and beta-3-tubulin.

<p>Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to the combination of c-Myc and beta-3-tubulin.</p

Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to beta-3-tubulin.

<p>Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to beta-3-tubulin.</p

Univariate analysis for Event Free Survival (EFS).

<p>vs: versus; G: grade; IHC: immunohistochemistry.</p><p>Univariate analysis for Event Free Survival (EFS).</p

Outcome results according to tumor size and nodal involvement.

<p>DFS: disease free survival; OS: overall survival; yrs: years; n.e.: not evaluable (too few patients).</p><p>Outcome results according to tumor size and nodal involvement.</p

Univariate analysis for Overall Survival (OS).

<p>vs: versus; G: grade; IHC: immunohistochemistry.</p><p>Univariate analysis for Overall Survival (OS).</p

Patients’ characteristics, according to clinicopathological and molecular variables.

<p>G: grade; TUR: trans-urethral resection; IHC: immunohistochemistry. Among 46 cancer, 36 showed urothelial, 2 squamous, 2 sarcomatoid, 2 micropapillary, 1 squamo-glandular, 1 small cell, 1 nested, 1 plasmocytoid differentiation.</p><p>Patients’ characteristics, according to clinicopathological and molecular variables.</p

A] c-Myc iperexpression (2+); B] absence of expression of c-Myc.

<p>A] c-Myc iperexpression (2+); B] absence of expression of c-Myc.</p

Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

<div><p>Background</p><p>The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research.</p><p>Methods</p><p>Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI). Interaction test according to tumor PD-L1 was accomplished. A sensitivity analysis according to adopted drug, tumor type, PD-L1 cut-off and treatment line was performed.</p><p>Results</p><p>Twenty trials (1,475 patients) were identified. A significant interaction (<i>p<0</i>.<i>0001</i>) according to tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% (95% CI 27.6-41.3%) in the PD-L1 positive and 19.9% (95% CI 15.4-25.3%) in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivolumab and pembrolizumab, with an absolute difference of 16.4% and 19.5%, respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLC, respectively, with no significant difference for genitourinary cancer.</p><p>Conclusion</p><p>Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC.</p></div

Results of the sensitivity analysis.

<p><i>Panel [A]</i>: overall response rate, with 95% confidence interval in square brackets, according to PD-L1 expression cut-off; <i>Panel [B]</i>: overall response rate with 95% confidence interval in square brackets, according to treatment line. Chi²: Chi-square test; PD-L1: programmed death-ligand-1.</p