Summary: New research from Flinders University shows that people with higher body mass index (BMI) receiving atezolizumab for advanced non-small cell lung cancer (NSCLC) experienced improved survival rates compared with those with lower BMI.
Source: Flinders University
Key finding: Although a higher BMI is usually associated with greater risk for many diseases including some cancers, diabetes and cardiovascular disease, this study found that patients with elevated BMI had better outcomes when treated with the immune checkpoint inhibitor atezolizumab for NSCLC.
Researchers from Flinders University analyzed individual patient data from four international clinical trials of atezolizumab, an immunotherapy increasingly used to treat advanced non–small cell lung cancer. Their pooled analysis revealed a clear association between higher baseline BMI and improved overall survival in patients treated with atezolizumab, an effect that was not observed in patients treated with the chemotherapy agent docetaxel.
The results, published in JAMA Oncology, add to a growing body of literature discussing the so‑called “obesity paradox,” where excess body weight is linked to higher risk of disease development yet, paradoxically, can sometimes be associated with better outcomes for certain treatments. Lead investigator Dr Ganessan Kichenadasse and colleagues suggest that the interaction between BMI, systemic inflammation and immune response may underlie the improved response to immune checkpoint inhibitor (ICI) therapy in patients with higher BMI.
In the pooled dataset used for analysis, 2,110 patients from four trials had adequate baseline and outcome information. Of those, 1,434 patients received atezolizumab and 676 received docetaxel. Across the atezolizumab-treated group, 49% were classified as normal weight, 34% as overweight and 7% as obese. The statistical analysis demonstrated a linear relationship between increasing BMI and improved overall survival among patients treated with atezolizumab, even after adjusting for key confounding variables.
Importantly, the association between higher BMI and better outcomes was strongest in patients whose tumors had high PD‑L1 expression, suggesting that BMI may interact with tumor immune environment to influence response to ICI therapy. For example, in the subgroup with the highest PD‑L1 expression, patients with obesity had a substantially lower hazard of death compared with lower BMI groups. Progression‑free survival was also improved among overweight and obese patients in this high PD‑L1 subgroup. Treatment-related adverse events were not found to be associated with BMI.
“While our study only assessed BMI at baseline and during treatment, these findings support further investigation into how BMI and related inflammatory or metabolic factors may influence response to cancer immunotherapy,” says Dr Ganessan Kichenadasse.
The researchers caution that these results do not negate the well‑established public health warnings about overweight and obesity. The World Health Organization estimates that millions of deaths each year are attributable to excess body weight, which increases the risk of coronary heart disease, stroke, type 2 diabetes and other conditions. However, within the specific context of ICI therapy for advanced NSCLC, baseline BMI may prove to be an informative factor when studying and designing future clinical trials.
Of the 1,434 patients treated with atezolizumab in this analysis, the median age was 64 years and 62% were male. The pooled analysis used data from two single-arm phase 2 trials and two randomized trials, with data cutoffs ranging from 2015 to 2016. The control arm in the randomized trials received docetaxel every three weeks until progression or unacceptable toxicity, while the experimental arms received atezolizumab on the same schedule under trial protocols.
Funding: The research received partial funding from Cancer Council of South Australia.
Source:
Flinders University
Media contact:
Ganessan Kichenadasse – Flinders University
Image source:
Image in the public domain.
Original research (closed access):
“Association between body mass index (BMI) and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer: analysis of atezolizumab clinical trials.” Ganessan Kichenadasse, John O. Miners, Arduino A. Mangoni, Andrew Rowland, Ashley M. Hopkins, Michael J. Sorich. Published in JAMA Oncology.
Abstract (summary)
Importance:
Previous evidence suggested high BMI might be associated with survival benefit from immune checkpoint inhibitors in melanoma; whether a similar association exists for advanced non–small cell lung cancer treated with atezolizumab was previously unknown.
Objective:
To evaluate associations between BMI and survival outcomes and treatment-related adverse events in patients with advanced NSCLC treated with atezolizumab.
Design, setting and participants:
A pooled analysis of individual patient‑level data from four international multicenter clinical trials—two single‑arm phase 2 trials and two randomized trials—evaluated patients with measurable advanced NSCLC who were either treatment‑naïve or previously treated. Analyses were performed on data collected between 2015 and 2016, with pooled analysis completed in 2019.
Interventions:
Patients received either atezolizumab every three weeks or, in the control arms of the randomized trials, docetaxel every three weeks until progression or intolerable toxicity.
Main outcomes:
Associations between BMI and overall survival (OS), progression‑free survival (PFS), and treatment‑related adverse events were examined using intention‑to‑treat principles.
Results:
Among evaluable patients, obesity (BMI ≥ 30 kg/m2) was independently associated with improved overall survival in those treated with atezolizumab but not in those treated with docetaxel, after adjustment for confounders. The association was strongest in patients with high PD‑L1 expression. No link between BMI and the rate of treatment‑related adverse events was observed.
Conclusions and relevance:
High BMI appears independently associated with better survival outcomes in NSCLC patients treated with atezolizumab. These findings suggest baseline BMI might be considered as a stratification factor in future trials of immune checkpoint inhibitors and point to the need for more research into biological mechanisms that could explain this relationship.