Lead Investigator: Feng Sun, Peking University
Title of Proposal Research: An individual participant data meta-analysis to evaluate PD1 vs PD-L1 Inhibitors in Asian subgroup Cancer patients
Vivli Data Request: 7824
Funding Source: China National Natural Science Foundation(no.72074011)
Potential Conflicts of Interest: Feng Sun has no conflicts of interest with the Adverse Reaction Monitoring Center of Beijing now, she had several scientific research projects which were founded by the Adverse Reaction Monitoring Center of Beijing previously, and all of them had final results, which was not related to the current study.
Summary of the Proposed Research:
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.
Requested Studies:
Phase 1/2a Study of Double-Immune Suppression Blockade By Combining a CSF1R Inhibitor (PLX3397) With An Anti-PD-1 Antibody (Pembrolizumab) To Treat Advanced Melanoma And Other Solid Tumors
Data Contributor: Daiichi Sankyo
Study ID: NCT02452424
Sponsor ID: PLX108-14
A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Data Contributor: Roche
Study ID: NCT03434379
Sponsor ID: YO40245
A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02951767
Sponsor ID: GO29293 (Cohort 1)
A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab and Taxane Based Therapy
Data Contributor: Roche
Study ID: NCT02924883
Sponsor ID: WO30085
A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Data Contributor: Roche
Study ID: NCT02908672
Sponsor ID: CO39262
A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02763579
Sponsor ID: GO30081
A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Data Contributor: Roche
Study ID: NCT02420821
Sponsor ID: WO29637
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 Multistage, Phase II Study Evaluating the Safety and Efficacy of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as First-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer
Data Contributor: Roche
Study ID: NCT02322814
Sponsor ID: WO29479
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02302807
Sponsor ID: GO29294
A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02108652
Sponsor ID: GO29293 (Cohort 2)
A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02031458
Sponsor ID: GO28754
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
A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Data Contributor: Roche
Study ID: NCT01984242
Sponsor ID: WO29074
A Phase II, Open-label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti−PD-L1 Antibody) Compared With Docetaxel in Patients With Non−Small Cell Lung Cancer After Platinum Failure
Data Contributor: Roche
Study ID: NCT01903993
Sponsor ID: GO28753
A Phase II, Multicenter, Single-arm Study of MPDL3280A in Patients With PD-L1-Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT01846416
Sponsor ID: GO28625
Update: This data request was withdrawn on 23-Aug-2024 by the researcher.