Lead Investigator: Alberto Martini, San Raffaele University
Title of Proposal Research: Role of body mass index and Beta Blockers in metastatic urothelial carcinoma
Vivli Data Request: 7078
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
The obesity paradox is a peculiar phenomenon whereby patients that are obese tend to survive longer, if affected by certain diseases, such as cancer.
While this phenomenon has been demonstrated in certain malignancies, the obesity paradox in patients with metastatic urothelial carcinoma (e.g. bladder cancer that has spread to other parts of the body) has not yet been investigated. If proven true, body mass index (BMI) categories, as per the World Health Organization (WHO), could represent a novel stratification factor for randomization for patients enrolled in future prospective trials and aid in study design.
Beta blockers are medications that are given to treat hypertension or following coronary artery disease (e.g. miocardial infaction). It has been demonstrated in patients with metastatic melanoma a synergistic effect of beta blockers and immunotherapy, meaning that patients that receive beta blockers and are on immunotherapy tend to achieve a greater degree of response to immunothreapy. This is due to the fact that beta blockers can enhance the activity of white blood cells that are the same target of immunotherapy for cancer. If proven true, in the context of metastatic urothelial carcinoma, one could advise on the use of beta blockers to all patients with hypertension or coronary syndromes instead of other alternative medications.
Statistical Analysis Plan:
The investigator seeks to analyze the role of BMI and outcomes. The role of BMI will be investigated as a continuous and as a categorical variable on survival and progression-free survival by means of the Cox regression or the Fine and Gray regression, if data on cancer speciﬁc mortality and other cause mortality is available. Survival curves will be plotted according to the Kaplan-Meier method for overall survival and to the competing risks method for cancer specific mortality, if available. Similarly, the role of beta blockers on outcomes will be investigated through the same methodology. Patients with missing values on BMI or the use of beta blockers will not be considered for the analyses’ purposes. A study population will be used to test the aforementioned hypotheses and the other one for validation.
Data on comorbidities, medical therapies at the time of randomization, survival and response outcomes will be necessary to carry out the proposed study.
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)
- Robesti D, Nocera L, Belladelli F, Schultz JG, Fallara G, Marandino L, Raggi D, Montorsi F, Necchi A, Martini A. PD09-11 THE IMMUNE-RELATED ADVERSE EVENTS PARADOX IN LOCALLY ADVANCED OR METASTATIC UROTHELIAL CANCER PATIENTS RECEIVING ATEZOLIZUMAB: ANALYSIS OF INDIVIDUAL PARTICIPANT DATA FROM IMvigor210 AND IMvigor211. The Journal of Urology. 2023 Apr;209(Supplement 4):page e244. doi: 10.1097/JU.0000000000003240.11
- Robesti D, Nocera L, Belladelli F, Schultz JG, Fallara G, Marandino L, Raggi D, Montorsi F, Msaouel P, Necchi A, Martini A. The immune‐related adverse events paradox in locally advanced or metastatic urothelial cancer after atezolizumab immunotherapy: Analysis of individual patient data from IMvigor210 and IMvigor211 Trials. BJU international. doi: 10.1111/bju.16121