DOI: 10.25934/pr00007824
title: An individual participant data meta-analysis to evaluate PD1 vs PD-L1 Inhibitors in Asian subgroup Cancer patients

description: Cancer ranks as a leading cause of death and an important barrier to increasing life expectancy in every country of the world. Newly published data indicated that there were an estimated 19.3 million new cases and 10 million cancer deaths a year worldwide. “Squamous non-small cell lung cancer” is one of the pathological subtypes of lung cancer. Lung cancer can be divided into several pathological subtypes, such as epithelial tumors, mesenchymal tumors, lymphohistiocytic tumors, et al. Moreover, epithelial tumors can be reclassified into adenocarcinoma, squamous cell carcinoma, small cell carcinoma, non-small cell carcinoma, et al. Squamous non-small cell lung cancer is a certain subtype of lung cancer pathological diagnosis.

Remarkable progress had led to a paradigm shift in cancer treatment, represented by immunotherapy as immune check-point inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1), which is a type of drug that blocks proteins called checkpoints that are made by some types of immune system cells, such as T cells, and some cancer cells and these checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells. PD1 and PD-L1 are two of the immune checkpoint biomarkers expressed on the surface of T cells or cancer cells, the biologic function of these biomarkers is to help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells. Thus, PD1 and PD-L1 are natural targets of drug development, PD1 inhibitors and PD-L1 inhibitors are two classes of immunotherapy drugs, which are also called immune checkpoint inhibitors. Besides, immune checkpoint also includes such as CTLA-4, and CLTA-4 inhibitor Ipilimumab also called immune checkpoint inhibitor as well.

With the rapidly increasing numbers of studies in immunotherapy but lack of head-to head comparisons, which can be integrated to obtain high-quality evidence, differences between the efficacy and safety of anti–PD-1 and anti–PD-L1 emerged to be reported. For example, two large-scaled randomized controlled trials (RCTs, KEYNOTE-407 and IMpower131) had controversial results of anti–PD-1 (pembrolizumab) or anti–PD-L1 (atezolizumab) plus chemotherapy in squamous non–small cell lung cancer. Such disparities have attracted widespread attention by clinicians, and there is a need to better understand the similarities and differences between anti–PD-1 and anti–PD-L1 for the ultimate benefit of patients with cancer.

Moreover, there is a large population of cancer patients in Asia countries such as China, but most RCTs of these immunotherapy drugs were carried out in western populations. Whether the conclusions of these RCTs can be verified in Asia population is an essential question. Considering that the efficacy and safety of drugs may be affected by many factors, drugs may have different effects on patients with different baseline characteristics. The integration of evidence among Asia/ Chinese population is of great significance to duplicate and verify the effectiveness of RCTs in Chinese real-world studies.

Using individual participant data to do systematic review and meta-analysis (A systematic review answers a defined research question by collecting and summarizing all empirical evidence that fits pre-specified eligibility criteria. A meta-analysis is the use of statistical methods to summarize the results of these studies.) and come to the efficacy and safety results, which is the highest quality evidence, is the “golden standard” of evidence-based medicine. We want to obtain the individual participant data to do systematic review and meta-analysis in specific sub-groups among Asian Cancer patients and to further determine which kind of immunotherapy is more suitable for different sub-group cancer patients.