The aim of this study is to evaluate the effect of a probiotic supplement containing Bifidobacterium animalis lactis BL-04 on the clinical effectiveness of immunotherapy in patients diagnosed with metastatic non-small cell lung cancer who are receiving immunotherapy.
Despite modern treatments, lung cancer remains a leading cause of high mortality worldwide. Over the past decade, significant improvements in patient survival have been achieved with immune checkpoint inhibitors, which enhance the T cell-mediated immune response to eradicate cancer cells. However, therapeutic resistance, drug side effects, and heterogeneous treatment responses limit their effectiveness. Recent studies have established a clear relationship between gut microbiota and cancer immunotherapy. The intestinal microbiota has been shown to stimulate the anti-tumor immune response by modulating immune system cells. Evidence from preclinical and clinical studies indicates that gut microbiota plays a crucial role in the efficacy of immunotherapy and the modulation of drug toxicity. Identifying the microbiota as a potential biomarker could facilitate personalized treatment protocols. Genetic, epigenetic, and microbiota modulation factors are essential for optimizing cancer immunotherapy outcomes. Consequently, research is increasingly focusing on personalized treatment protocols for microbiota modulation, including diet regulation, fecal microbiota transfer, prebiotics, and probiotics. There has been a significant rise in studies demonstrating the clinical benefits of microbial therapy products as complementary treatments. The functional role of microbiota in modulating the systemic immune response has prompted investigations into its impact on cancer immunotherapy, particularly with agents targeting immunological checkpoints like PD-1. Recent studies have identified both positive and negative regulatory bacteria that influence immunotherapy effectiveness. However, sociocultural and dietary lifestyle differences affect gut microbiota composition, leading to variations between populations. Therefore, studies are needed to identify the unique microbiome composition of each population to develop microbiota biological indicators for cancer immunotherapy. No research has been conducted in this area in Türkiye. This study aims to identify bacterial species that may serve as biomarkers for the microbiota specific to Turkish cancer patients receiving immunotherapy and use them for prognostic purposes. Understanding the significant role of probiotics in modulating intestinal microbiota has increased the demand for these food supplements. Studies show that anti-tumor efficacy is specific to the bacterial strain. For instance, Bifidobacteriums have been reported to enhance the effectiveness of PD-1 blockers in experimental rat models. In another study, B. lactis BL-04 reduced immunotherapy-induced colitis in animals. This study will investigate the effect of a probiotic supplement containing Bifidobacterium animalis lactis BL-04 on clinical objective response, clinical benefit rates, and intestinal microbiota in patients with metastatic non-small cell lung cancer (mNSCLC) receiving nivolumab. The results may facilitate the development of specific probiotic supplements as a complementary therapy for mNSCLC treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
100
4 x 10\^9 cfu/g/day Bifidobacterium animalis subsp. lactis Bl-04 for 12 weeks
1 g/day maltodextrin for 12 weeks
Necmettin Erbakan University
Konya, Turkey (Türkiye)
RECRUITINGEvaluation of Clinical Response
The clinical impact of the immunotherapy will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria based on radiological analysis.
Time frame: Week 12
Progression-free survival
The progression-free survival (PFS) period will be defined as the interval between the initiation of treatment and the date of radiological progression.
Time frame: Basaline and the date of radiological progression
Overall survival
The overall survival (OS) period will be defined as the interval between the date of disease diagnosis and death from any cause.
Time frame: Basaline and the date of death from any case
Intestinal microbiota modulation
Microbiota and fatty acid analyses, including acetic acid, propionic acid, and butyric acid, will be conducted on fecal samples."
Time frame: Basaline and Week 12
Immunological findings
The concentrations of CD4+ T cell subgroups (Th1, Th2, Th9, Th17, Th1Th17, and Treg) and sitokins (IL-1β, IL-4, IL-10, IL-17, TNF-α, TGF-beta, IFN-gamma, IL-36 and trimethylamine N-oxide) will be quantified in the serum samples of the patients.
Time frame: Basaline and Week 12
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