In a study reported in JAMA Oncology, Kichenadasse et al found that high body mass index was associated with improved overall survival in patients with advanced non–small cell lung cancer (NSCLC) treated with atezolizumab.
“High BMI appears to be independently associated with improved survival with atezolizumab in patients with NSCLC, raising the possibility that baseline BMI should be considered as a stratification factor in future immune checkpoint inhibitor therapy trials.”— Kichenadasse et al
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As noted by the investigators, there are data showing that high BMI is associated with improved survival in patients with melanoma receiving immune checkpoint inhibitor therapy as well.
Study Details
The study involved pooled analysis of patient-level data from two single-arm phase II trials (BIRCH and FIR), one phase II randomized trial (POPLAR), and one phase III randomized trial (OAK). Patients had previously untreated advanced NSCLC or had received at least one line of systemic therapy. Adequate data were available for 2,110 patients (of a total of 2,261) from the four trials; of these, 1,434 received atezolizumab every 3 weeks and 676 received docetaxel every 3 weeks. Normal weight, overweight, and obesity were defined as BMI of 18.5–24.9, 25.0–29.9, and ≥ 30 kg/m2, respectively.
Key Findings
Among patients receiving atezolizumab, overall survival was significantly improved (overall P < .001) among those classified as obese (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.51–0.81) and overweight (HR = 0.81, 95% CI = 0.68–0.95) compared with those who were of a normal weight.
The overall survival benefit in the atezolizumab group was greater (overall P < .001) among obese (HR = 0.48, 95% CI = 0.34–0.66) and overweight (HR = 0.73, 95% CI = 0.58–0.91) patients vs normal weight patients with programmed cell death ligand 1 (PD-L1)-positive disease. Benefit was greatest among patients with the highest category of PD-L1 expression (≥ 50% of tumor cells or ≥ 10% of tumor-infiltrating immune cells; n = 436), with hazard ratios of 0.36 (95% CI = 0.21–0.62) for obesity and 0.69 (95% CI = 0.48–0.98) for overweight.
KEY POINTS
- Among patients receiving atezolizumab, overall survival was significantly improved among those classified as obese and overweight compared with those who were of a normal weight.
- The overall survival benefit in the atezolizumab group was greater among obese and overweight patients vs normal weight patients with PD-L1–positive disease.
- Improvements in progression-free survival among patients classified as overweight or obese did not achieve statistical significance.
Improvements in progression-free survival among patients classified as overweight (HR =0.89, 95% CI = 0.78–1.01) or obese (HR = 0.86, 95% CI = 0.73–1.01) did not achieve statistical significance (overall P = .09).
In the docetaxel group, no significant effect on overall survival was observed with obesity (HR = 0.92, 95% CI = 0.70–1.21) or overweight (HR = 0.96, 95% CI = 0.78–1.18) vs normal weight status (overall P = .82).
No association between treatment-related adverse events and BMI was observed.
The investigators concluded, “High BMI appears to be independently associated with improved survival with atezolizumab in patients with NSCLC, raising the possibility that baseline BMI should be considered as a stratification factor in future immune checkpoint inhibitor therapy trials.”
Ganessan Kichenadasse, FRACP, of Flinders Medical Centre, Flinders University, Australia, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from Cancer Council South Australia and National Breast Cancer Foundation. For full disclosures of the study authors, visit jamanetwork.com.
