Hakaru Tadokoro

The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis.

BACKGROUND Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. METHODS We assessed the potential role of PD-L1 expression according to Cochrane Collaborations Guidelines. RESULTS 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearsons correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). CONCLUSION Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data

AIM The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. METHODS We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. RESULTS 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). CONCLUSION PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker.

BACKGROUND Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. CONCLUSIONS The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

Background Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. Design We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. Results We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were

Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging sequencing for new treatment targets

155 605 and

EGFR and EML4-ALK Updated Therapies in Non-Small Cell Lung Cancer.

187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was

Small Intestine Cancer

215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was

P2.45: An Estimate of the Economic Impact of Treatment of NSCLC With Immunotherapy Relative to PD-L1 Expression in Brazil: Track: Immunotherapy

98 421. Patient selection also reduced the budget impact of immunotherapy. Conclusion The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.

O.03: Cost Effectiveness of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Relative to PD-L1 Expression

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of non-small cell lung cancer (NSCLC) after failure of platinum-based therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events.

Current advances in targeted therapies for metastatic gastric cancer: improving patient care

BACKGROUND Non-small cell lung cancer is the leading cancer-related cause of death. OBJECTIVE We review the latest therapies for NSCLC with EGFR and ELM4-ALK mutations as well as the most relevant studies and promising patents. METHOD A literature search of PubMed database was carried out to identify recent Clinical Trials using EGFR therapies and novel patents involving diagnosis and therapies on NSCLC. We conducted a search to find new therapy strategies, new biomarkers, and selected five patents we find relevant. RESULTS Over the last few years, identification of cancer harboring epidermal growth factor receptor mutations (EGFR) or chromosomal rearrangements of anaplastic lymphoma kinase (ALK) led to new ways in classifying and treating NSCLC. On the other hand, acquired resistance are a constantly challenge in the management of patients with these mutations and new drugs options are in development to improve and amplify treatment strategies. CONCLUSIONS Currently, EGFR TKIs (e.g.: erlotinib, gefitinib, osimertinib) and ALK inhibitors (crizotinib, ceritinib, alectinib) provided a new face for advanced NSCLC outcomes. To understand the disease molecular profile is mandatory to define the best approach for each patient.