Lead Investigator: Kazuki Takada, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
Title of Proposal Research: Impact of Probiotics on Clinical Outcomes in Patients with Extensive-Stage Small-Cell Lung Cancer Treated with First-Line Atezolizumab Combination Therapy A Post Hoc Analysis of IMpower133
Vivli Data Request: 9244
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Small-Cell Lung Cancer (SCLC) represents about 10-15% of all lung cancers and is a rapidly progressing and challenging type to treat. The 5-year survival rate for this disease is very low, and due to the difficulty of early diagnosis, many cases are already advanced by the time of detection. Limited-stage SCLC presents only on one side of the chest and extensive-stage SCLC (ES-SCLC) has spread widely throughout the lung, to the other lung, to lymph nodes on the other side of the chest, or to other parts of the body (including the bone marrow). ES-SCLC remains an important challenge in oncology, as reported in the IMpower133 clinical trial, in which the immune checkpoint inhibitor atezolizumab (checkpoint inhibitors are immunotherapy drugs that stop tumors from evading white blood cells and stimulate an immune response against the tumor cells) was combined with carboplatin and etoposide (types of chemotherapy drugs which attach to tumor cells and stop them growing and dividing), has brought new hope to these patients. However, the prognosis of ES-SCLC remains poor and further treatment development is urgently needed to improve prognosis.
In recent years, it has been suggested that the gut microbiota (microorganisms that live in the digestive tract) plays a pivotal role in determining the efficacy of immunotherapy in many carcinomas. However, the interaction of the gastrointestinal environment, particularly the influence of probiotics (foods or supplements that contain live microorganisms intended to maintain or improve the “good” bacteria in the body), on the efficacy of cancer immunotherapy in ES-SCLC is not well understood.
The aim of this post hoc analysis of the IMpower133 clinical trial data is to ascertain the impact of probiotics on the clinical outcomes in patients with ES-SCLC treated with first-line atezolizumab combination therapy.
Statistical Analysis Plan:
The objective of this post hoc analysis of the IMpower133 clinical trial data is to ascertain the impact of probiotics on the clinical outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with first-line atezolizumab combination therapy. IMpower133 clinical trial was a randomized trial of atezolizumab plus carboplatin and etoposide vs placebo plus carboplatin and etoposide for patients with chemotherapy-naive ES-SCLC. The research population will include both the treatment arm and the control arm. Patients with missing data will be excluded from the analysis (complete case analysis). Analyses adjusted for factors such as age, sex, race/ethnicity, smoking history/status, ECOG performance status, body mass index, the presence of liver, central nervous system and bone metastasis, antibiotic use, and proton pump inhibitor use will be conducted. The association between probiotics use and both progression-free survival and overall survival will be assessed in the participants from the treatment arm and in those from the control arm, respectively, using the Kaplan-Meier method with the log-rank test and Cox proportional hazards regression analysis. Hazard ratios and 95% confidence intervals will be estimated using Cox proportional hazards regression analysis. If the proportional hazards assumption is not met, we will perform an analysis using restricted mean survival time. If the number of patients on probiotics is small, the analysis will be adjusted for patient background using a propensity score. Statistical significance will be considered at a p-value of less than 0.05.
Patient demographics and baseline characteristics will be summarized using descriptive statistics or contingency tables. The Pearson’s chi-squared test will be used for categorical variables, and either the independent t-test or Kruskal-Wallis test will be used for continuous variables to test baseline associations.
All statistical analyses will be conducted using either R software or SAS software.
Requested Studies:
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
Public Disclosures:
Takada, K., Takamori, S., Shimokawa, M., Pinato, D.J. and Cortellini, A., Prior antibiotics, proton pump inhibitors, and probiotics in patients with extensive stage small cell lung cancer treated with immune checkpoint blockade: A post-hoc analysis of the phase I/III IMpower 133 trial. International journal of cancer. Doi : 10.1002/ijc.35249