Center for Global Research Data

An Investigation on the Role of Blood Biomarkers as Predictors for Individualized Treatment Regimen Selection in Non-Small Cell Lung Cancer.

Lead Investigator: Yang Zhao, Nanjing Medical University
Title of Proposal Research: An Investigation on the Role of Blood Biomarkers as Predictors for Individualized Treatment Regimen Selection in Non-Small Cell Lung Cancer.
Vivli Data Request: 7492
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:
Lung cancer is one of the most common causes of death worldwide accounting for 1.80 million deaths in 2020 and its incidence is still increasing. Non-small cell lung cancer (NSCLC) accounts for about 80 to 85 percent of lung malignancies. There are many important medicines to prolong patients’ lifetime and improve their life quality. PD-1 is a protein found on the surface of T-cells in the immune system. When PD-1 binds to PD-L1 on the surface of the cancer cell, it enables cancer cell to “hide” from an immune attack. Monoclonal antibodies, such as Atezolizumab, target PD-L1 to block this binding and boost the immune response against cancer cells. Immunotherapies of cancer focus on moving the balance from a pro-tumor to an antitumor microenvironment. Finally, this change allows the immune system to maximize an efficient antitumor response. But until now, we do not have much knowledge about the role of various components in the tumor microenvironment when NSCLC patients are treated with Atezolizumab.

Blood biomarkers, measurable indicators of some biological state or condition, are often used to reflect microenvironment, including neutrophils (a type of white blood cells), lymphocytes (a type of immune cell), platelets (a type of blood cells reacting to stop bleeding) and blood sodium, etc. Previous research showed that the level of potassium in the blood had some influence on the anti-tumor T cells. Elevated blood potassium would constrain the metabolism of T cells and further resulted in reduced immunity and cancer progression. Our previous meta-analysis claimed higher objective response rate and disease control rate could be observed in patients with lower blood potassium. However, there was no research reporting this relationship in the treatment with Atezolizumab. Some research also claimed that neutrophil to lymphocyte ratio and platelet-lymphocyte ratio, dynamic inflammatory biomarkers reflecting the real-time status of immune system, were useful predictors of treatment effect in NSCLC but with limited sample size. Clinical trials data could reflect the changing patterns of blood biomarkers with strict follow up during the treatment of Atezolizumab in NSCLC. Statistical models, such as Cox proportional hazards model, will be used to explore the association between blood biomarker levels and treatment effect (e.g., overall survival, disease free survival, etc.) of Atezolizumab.

Better understanding about the association even the causation between blood biomarkers and treatment effect could help doctors predict the treatment response and provide evidence for personalized selection of treatment regimen in precision medicine.

Requested Studies:

A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367794
Sponsor ID: GO29437

A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367781
Sponsor ID: GO29537

A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02366143
Sponsor ID: GO29436

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02008227
Sponsor ID: GO28915