Improved survival with elevated BMI following immune checkpoint inhibition across various solid tumor cancer types

Abstract

Introduction/background: Obesity is a well-known risk factor for various cancers, yet emerging research demonstrates its association with improved survival outcomes in cancer treatment, labeled as "the obesity paradox." Studies investigating the clinical benefits of obesity across various cancer types after immune checkpoint inhibition (ICI) are limited.

Methods: Data were queried from the TriNetX database to identify patients with solid tumor malignancies of various organ systems (pulmonary/intrathoracic, cutaneous, head and neck, gastrointestinal, breast, genitourinary) who received ICI between 2012 and 2024. Propensity score matching was used to match cohorts for demographics, medical comorbidities, and oncologic staging. Primary outcome was overall survival (OS) up to 5 years and compared between obese body mass index (BMI; >30) and normal BMI (20-24.9) cohorts.

Results: After propensity score matching, there were a total of 18,434 patients, with 9217 patients in the obese BMI cohort and 9217 patients in the normal BMI cohort for all solid tumor malignancies. In the overall pan-cancer analysis, obese BMI was associated with significantly improved OS up to 5 years compared to the normal BMI cohort (hazard ratio [HR], 0.69 [0.66-0.72]). Subgroup analysis likewise demonstrated that obese BMI was associated with significantly improved OS up to 5 years for respiratory/intrathoracic (HR, 0.77 [0.72-0.83]), cutaneous (HR, 0.62 [0.63-0.78]), head and neck (HR, 0.67 [0.58-0.78]), gastrointestinal (HR, 0.67 [0.58-0.78]), breast (HR, 0.66 [0.55-0.79]), and genitourinary (HR, 0.57 [0.34-0.93]) malignancies (though not renal cell carcinoma specifically.) CONCLUSIONS: Obesity was associated with improved 5-year OS after treatment with ICI across various solid tumor malignancies in this electronic health record-based big data study. Further investigation is warranted to understand the mechanism of this association.

Keywords: immune checkpoint inhibition; obesity; overall survival; solid tumors.

FIGURE 1

Kaplan‐Meier survival curves depicting overall survival up to 5 years posttreatment with immune checkpoint inhibition between the obese (purple) and normal (green) BMI cohorts for the (A) overall pan‐cancer analysis and malignancies of the following organ systems; (B) pulmonary/intrathoracic; (C) cutaneous; (D) head and neck; (E) gastrointestinal; (F) breast; and (G) genitourinary.