Additional file 1: of Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study

Supplementary material and results. (DOC 60 kb

Additional file 1: of Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab

Table S1A. Cox regression models on overall survival in patients with brain metastases (DOCX 15 kb

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

Additional file 2: of Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab

Figure S1. Kaplan-Maier OS and PFS curves of melanoma patient treated with nivolumab. (A) Patients stratified according baseline median ANC as cutoff . Green line: ANC≥5.4; Blue line: ANC<5.4. (B) Patients stratified for PFS according baseline median ANC as cut-off . Green line: ANC≥5.4; Blue line: ANC<5.4. Figure S2. Kaplan-Maier OS and PFS curves of melanoma patient treated with nivolumab using optimal cutoff for derived neutrophils-to lymphocyte ratio (dNLR). (A)) Patients stratified according baseline dNLR. Green line: dNLR≥3.8; Blue line: dNLR<3.8. (DOCX 168 kb

Results of the sensitivity analysis—Overall response rate, with 95% confidence interval in square brackets, according to tumor type.

<p>Chi²: Chi-square test; PD-L1: programmed death-ligand-1; NSCLC: non-small cell lung cancer.</p

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

Results of the event rate analysis.

<p>ORR: overall response rate; CI: confidence interval; PD-L1: programmed death-ligand-1.</p

Results of the sensitivity analysis—Overall response rate, with 95% confidence interval in square brackets, according to adopted drug.

<p>Chi²: Chi-square test; PD-L1: programmed death-ligand-1.</p

Outline of the search—Flow chart of the studies included in the analysis.

<p>Pts: patients; n: number; PD-L1: programmed death-ligand-1; IHC: immunohistochemistry; ORR: overall response rate; NSCLC: non-small cell lung cancer.</p

Clinical characteristics and oncological therapies.

<p>Clinical characteristics and oncological therapies.</p