Obesity paradox in non-small cell lung cancer (NSCLC) patients on immune checkpoint inhibitors: Real-world evidence using the global collaborative network database.
Authors: Oboseh John Ogedegbe, Olanipekun Lanny Ntukidem, Henry Becerra, Ayobami Gbenga Olafimihan, Chiamaka Elsie Nwachukwu, Shakirat Gold-Olufadi, Neharika Shrestha, Dosbai Saparov, Asfand Yar Cheema, Sakshi Bai, Hassan Ali, Shammas Bajwa, Tioluwani Ojo, Jerome Dallas Winegarden, Rishita Gupta
Journal: Journal of Clinical Oncology (2025)

e20624 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Immune checkpoint inhibitors (ICIs) have recently transformed the landscape of cancer management. Recent studies suggest that obesity may improve survival outcomes in some cancer types; however, there remains a dearth of data on the effect of obesity in cancer patients on ICIs. We aim to analyse and evaluate this relationship. Methods: This retrospective cohort population-based real-world study was obtained by querying the TriNetX Global Collaborative Network database. We identified patients with NSCLC who received ICI. The ICIs included pembrolizumab, nivolumab, cemiplimab, iplimumab, atezolizumab, durvalumab and avelumab. The patient population was divided into two cohorts: patients with a BMI between 18.5-29.9kg/m2 and 30.0-39.9kg/m2. Racial and demographic information was obtained. Propensity score matching was carried out to remove confounders. Patients were matched for medical comorbidities, including tobacco use, emphysema, asthma, Type 2 diabetes mellitus and bronchiectasis. Survival analysis was conducted using Kaplan-Meier and log-rank test. The primary outcome was survival (OS) for 1 and 5 years. The secondary outcomes were complications of NSCLC, which included hemoptysis, malignant pleural effusion, SVC syndrome, dysphagia, and complications of ICI therapy, including hepatitis, colitis, thyroiditis, pneumonitis and rash. Results: Before propensity score matching (PSM), significant demographic and comorbid disparities existed between the obesity BMI group (N = 6,854) and the normal BMI group (N = 1,546). After PSM, both cohorts exhibited strong similarities, with 1,545 patients in both cohorts. Mean age (69 years vs 64.7 years), male (56.6% vs 58.04%), white (55.75% vs 52.34%). The obesity BMI was associated with an improved OS at 1 year (hazard ratio [HR] 0.753 [95% CI, 0.671-0.844], p = 0.0295) and at 5 years (HR 0.687 [95% CI, 0.625-0.754], p = 0.0233) in patients treated with ICIs. Obesity BMI was also associated with a reduction in NSCLC complications, including dysphagia (odds ratio [OR] 0.711 [95% CI, 0.543-0.931], p = 0.013), SVC syndrome (OR 0.457 [95% CI, 0.230-0.909], p = 0.002). However, the differences in rates of other complications, including hemolysis and malignant pleural effusion, were insignificant. There was also no difference in the rates of immune-related adverse events (IRAEs) between both patient populations. Conclusions: Our retrospective population-based study found that obesity was associated with improved 1-year and 5-year OS compared to normal BMI. In addition, obesity was associated with reduced rates of complications such as dysphagia and SVC syndrome. It is pertinent to research these findings further to provide more holistic care for patients.