medwireNews: Being overweight or obese is associated with favorable survival outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with atezolizumab, research published in JAMA Oncology suggests.
“The present study adds to the emerging evidence that high BMI may be associated with cancer survival following immunotherapy,” write Ganessan Kichenadasse (Flinders Centre for Innovation in Cancer, Bedford Park, South Australia) and colleagues.
They add: “Baseline BMI should therefore be considered as a stratification factor in future immune checkpoint inhibitor therapy trials.”
The post-hoc analysis was based on data collected from four clinical trials – OAK, POPLAR, BIRCH, and FIR – and consisted of 1434 patients who were given atezolizumab and 676 patients given docetaxel as a second-line or later treatment.
A linear association was observed between increasing BMI and overall survival (OS) in patients treated with atezolizumab, whereby obese (≥30 kg/m2) and overweight (25–29.9 kg/m2) participants had a significantly reduced risk for death relative to their normal-weight (18.5–24.9 kg/m2) counterparts, with hazard ratios (HRs) of 0.64 and 0.81, respectively.
The relationship between BMI categories and survival was consistent for both men and women, but was stronger in patients with PD-L1-positive than negative tumors. Specifically, in the PD-L1-positive subgroup, the HRs for death were a significant 0.48 and 0.73 for the obese and overweight BMI categories, respectively, versus the normal-weight category, but no such significant association was observed in the PD-L1-negative subgroup.
The researchers additionally investigated progression-free survival (PFS), and found that when the obese and overweight groups were combined, the risk for progression or death was a significant 22% lower than for the normal-weight group. However, there was no significant relationship between BMI and PFS when the obese and overweight classes were analyzed separately.
And similar to the OS data, the association between BMI and PFS was “most apparent” in PD-L1-positive patients, with “little indication of association” in those negative for the biomarker, say the researchers.
There was no significant difference between the incidence of treatment-related and immune-related adverse events (irAEs) across the BMI categories, with the exception of a higher incidence of skin-related irAEs in overweight patients, who had a significantly 47% increased risk.
Of note, the association between BMI and OS appeared to be restricted to atezolizumab-treated patients, with no such association observed among docetaxel-treated patients, either in the overall analysis or the PD-L1 expression subgroups.
Kichenadasse and colleagues postulate that the influence of BMI on survival of atezolizumab-treated patients may be attributed to the T-cell dysfunction synonymous with obesity. They highlight that atezolizumab inhibits the PD-1/PD-L1 axis, and thus “might induce a favorable response in patients with obesity with an established T-cell exhausted state.”
The researchers say that “it is unclear based on our analyses whether BMI could be considered as a treatment effect modifier,” and future research “across all immune checkpoint inhibitor trials may provide adequate power to evaluate this question.”
However, they emphasize: “It is likely that a combination of clinical and biochemical markers may be required to more accurately characterize obesity,” considering that “BMI is a poor reflection of body fat distribution.”
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