Lead Investigator: Wenlong Zhong, Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSU）
Title of Proposal Research: The influence of antibiotics on survival outcomes for bladder cancer patients being treated with immune checkpoint inhibitor therapy
Vivli Data Request: 8588
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Bladder cancer is one of the most common malignant tumors of the male genitourinary system in many regions. Its high incidence, high recurrence rate, and high mortality seriously threaten people’s health and life.
In recent years, immunotherapy, a treatment that targets the tumor itself and enhances the ability of immune cells (especially T cells) to recognize and attack tumor cells, has played an increasingly important role in prolonging the survival of bladder cancer patients and has become an important part of treatment. Immunotherapy drugs (also known as immune checkpoint inhibitors, ICIs) include programmed death-ligand 1 (PD-L1) inhibitors and programmed cell death protein 1 (PD-1) inhibitors. Their pharmacological effects are that PD-L1 antibodies can bind to PD-L1 on the surface of tumor cells, PD-1 antibodies can bind to PD-1 on the surface of T cells, thereby reducing the binding between PD-L1 on the surface of tumor cells and PD-1 on the surface of T cells (this type of binding can inhibit the tumor-killing function of T cells), thus enhancing T cells ability to kill tumor cells.
However, in clinical trials, less than 30% of bladder cancer patients receiving immunotherapy benefit from treatment. It is becoming increasingly important to help patients optimize individualized treatment and improve response rates.
Multiple clinical studies involving more than 1800 patients have shown that broad-spectrum antibiotic (antibiotic that target multiple bacteria) have a negative impact on cancer patients receiving immunotherapy. In patients receiving immunotherapy, antibiotic use is associated with poorer response rates and survival rates. Currently, multiple meta-analyses (essentially, meta-analysis is a way to pool data from multiple sources in order to gain a more comprehensive understanding of a particular research question) have indicated that antibiotic may be a negative prognostic factor for malignancies treated with ICIs. However, due to different types of cancers, different exposure time windows for different antibiotics and different patient conditions themselves, these conclusions may have certain limitations. To further explore whether antibiotics will affect immune therapy for bladder cancer or not, it is necessary to deeply understand the specific use of antibiotics and patient conditions in the IMVIGOR 210 cohort. Analysis of this high-quality real-world cohort study is needed to address three questions: 1. Whether the use of antibiotics alone will affect immune therapy for bladder cancer, regardless of whether it is good or bad; 2. Whether the type of antibiotic will affect immune therapy for bladder cancer; 3. Whether the timing of antibiotic use will affect immune therapy for bladder cancer. We will analyze the survival time or disease-free survival time of patients in this cohort, as well as whether they used antibiotics, the type of antibiotics used, and the time window for antibiotic use. By summarizing and analyzing these data statistically, we aim to find the underlying correlations between these data, and answer these three questions above.
Analysis of this study will help us further clarify whether there is an association between antibiotic and immune therapy for bladder cancer, and also importantly, provide a solid preliminary basis for further research on its possible impact mechanisms to settle this problem. This study will provide guidance for the immune therapy plan of bladder cancer patients, including guiding the timing of antibiotic use during immune therapy, the type of antibiotic application or the combined use of certain adjuvants during anti-infection processes, in order to enhance the efficacy of immune therapy while reasonably controlling infections in immune therapy patients.
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)