DOI: 10.25934/pr00009285
title: Association of Body Mass Index (BMI) with Prognosis and Safety Profile of Atezolizumab

description: Obesity, a pervasive public health concern, is an excessive accumulation of body fat. The Body Mass Index (BMI) is a formula that uses weight and height to categorize individuals as normal, overweight, or obese. BMI serves as a generalized proxy for body fat and is a foundational measure in various epidemiological studies. In the past 3 decades, the global prevalence of obesity has increased by 27.5% in adults and 47.1% in children.

Numerous studies have signaled a linkage between elevated BMI and an increased risk and mortality of multiple diseases, such as diabetes, heart disease and cancer. Notably, the association between obesity and cancer has become an increasingly scrutinized domain. However, according to scientific research, there exists a phenomenon known as the ‘obesity paradox’, whereby obese patients have been found to have longer survival time than their thinner counterparts, particularly in cases of bladder cancer, non-small cell lung cancer and head and neck cancers. The potential similarity or difference of this association across various tumor types, therapy line types (different steps or stages in a treatment plan), and therapy modalities (the various methods and techniques used to treat cancer) and immunotherapy (leveraging the body's immune system to fight cancer) remains unproven.
Immunotherapies have dramatically improved prognosis over the past decade. Types of immunotherapy treatment encompass: therapeutic vaccines,

immune modulators: substances that help to regulate or normalize the immune system by enhancing or suppressing the immune response to help fight infections, cancer, and other diseases

autologous cellular therapies: The extraction of specific cells from the patient's own body.

and monoclonal antibodies: An antibody produced from a cell lineage made by cloning a unique white blood cell. 

Atezolizumab and Nivolumab are different monoclonal antibodies approved in many countries. They work by blocking proteins called programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1), which play a key role in the immune system. PD-1 is found on the surface of T cells (types of immune cells), while PD-L1 is present on the surface of various cells. When PD-1 on T cells binds to PD-L1 on other cells, it acts as a checkpoint, signaling to the T cell to suppress its activity. This interaction helps prevent the immune system from attacking healthy tissues. However, some cancer cells exploit this mechanism by overexpressing PD-L1, which can inhibit T cell activity and evade immune detection, allowing cancer to proliferate. Immunotherapies targeting PD-1 or PD-L1 aim to block this interaction, enhancing T cell activity against cancer cells and boosting the immune response against tumors.

Atezolizumab was incorporated into clinical practice as an important option for treatment of multiple cancers, including non-small cell lung cancer, bladder cancer and breast cancer. However, the clinical prognosis of patients treated with immune checkpoint inhibitors (ICIs, being a special category of monoclonal antibodies, unleash the immune system to combat cancer more effectively by inhibiting immune checkpoints, thereby preventing cancer cells from hiding from immune attacks) varied substantially among individuals. Given that only 15-60% of patients demonstrate a positive response to ICIs, there is a pressing need for extensive research on predictive biomarkers (measurable indicators of some biological state or condition which often used to measure and evaluate the progress of disease or the effects of treatment)
Immune-related adverse events (ir-AE), unique treatment-specific toxicities of ICIs, were reported as predictive of PD-1 and PD-L1 response across multiple solid tumors. Higher proportions of ir-AE were reported in obese patients when treated with Nivolumab 3 mg/kg in multiple tumors. It is not yet clear whether the observed relationship is specific to Nivolumab or if it also applies to Atezolizumab, or if it is due to the higher doses administered to obese patients. Therefore, further research focusing on patients treated with Atezolizumab is warranted.

In conclusion, we aim to explore the role of BMI in the prognosis and safety profile of patients treated with Atezolizumab, investigating the association between BMI and prognosis, the relationship between BMI and ir-AE, and the mediation of ir-AE in BMI and prognosis, by utilizing individual-level data from various trials across multiple cancers. It promotes clinical practice in prolonging patient survival and prognosis through lifestyle modifications, while also emphasizing, to a certain extent, the significance of rational nutritional management and weight control in cancer treatment. Additionally, this research holds clinical significance as it aids clinicians in identifying populations that may derive greater benefits, optimizing the therapeutic strategy and potentially improving patient outcomes.