Hello, my name is Finlay Thompson and this is a presentation about a study investigating the association of obesity with overall survival in metastatic non-small-cell lung cancer patients that are receiving first-line Pembrolizumab therapy. Pembrolizumab is an immunotherapy drug that can be used to treat metastatic non-small-cell lung cancer. However, whilst Pembrolizumab has been shown to be an effective treatment, a proportion of patients derive little clinical benefit. Biomarkers that predict whether patients are likely to respond or not would assist in clinical decision making and how best to manage these patients. The association of obesity with an increased incidence, progression and mortality in some cancers but a decreased mortality in other cancers has become termed the obesity paradox. However, it is unclear whether BMI measurement could be used as a biomarker in metastatic non-small-cell lung cancer patients. So, we investigated the association of obesity to the measurement of BMI with overall survival in patients receiving first-line Pembrolizumab for metastatic non-small-cell lung cancer. In the context of high obesity rates in Scotland and in the UK, this is an important association to investigate for this population of patients. In this single-centred retrospective cohort study, we collected pre-treatment body measurement data from all eligible patients and calculated BMI and categorised patients as obese or non-obese. These included all had metastatic non-small-cell lung cancer and a PD-L1 expression of greater than or equal to 50%. Furthermore, all patients were receiving first-line Pembrolizumab monotherapy. Data were available for 166 patients, 13.9% of which were categorised as obese. Our analysis showed that obese patients had a significantly longer overall survival in comparison to those defined as non-obese, as shown in this graph, with a median overall survival of 31 months in those with BMI greater than 30, in comparison to 11 months in those with a BMI of less than 30. However, the reason behind this positive association of obesity with overall survival in this group of patients is unclear. Possible explanations include that in the context of a dysfunctional immune state seen in obese patients, there is a greater efficacy of PD-1 blockade. The PD-1-mediated T-cell dysfunction in obesity leaves tumours markedly more responsive to checkpoint blockade through drugs such as Pembrolizumab, leading to a greater efficacy of these treatments. Another hypothesis is that obesity provides a larger physiological reserve that confers an advantage by slowing the progression of cachexia and helping endure anti-cancer treatments. Conversely, some have argued that this association may be actually due to a spurious relationship and may be due to methodological reasons such as reverse causality or due to confounding variables. Furthermore, BMI is a simple but flawed measurement of body composition. For example, it cannot differentiate between fat and lean mass. Other measures of body composition, such as sarcopenia and pre-diagnosis weight loss, may be more useful measurements and should be explored further. Our study showed that obesity is associated with longer survival in patients receiving first-line Pembrolizumab from metastatic non-small-cell lung cancer patients with a PD-L1 expression of greater than or equal to 50%. However, further research is needed to determine whether this is a true or spurious relationship and should investigate other measures of obesity and of body composition. Thank you very much.

obesity

overall survival

metastatic non-small-cell lung cancer

Pembrolizumab therapy

immune state