High BMI Associated With Improved Survival with Checkpoint Therapy for Lung Cancer

By Michael Vlessides, /alert Contributor
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A new study has found that high body mass index is independently associated with improved survival after atezolizumab therapy in patients with non small-cell lung cancer (NSCLC). 

As an Australian research team concluded, these findings raise the possibility that baseline BMI should be considered a potential stratification factor in future immune checkpoint inhibitor therapy trials.


BMI and obesity. Source: Getty

“High BMI is independently associated with overall survival benefit from immune checkpoint inhibitor therapy in patients with melanoma, yet whether BMI is associated with outcomes in patients with advanced NSCLC treated with atezolizumab remains unknown,” the authors wrote in a recent issue of JAMA Oncology.

To help answer this question, investigators from Flinders University in Bedford Park, Australia conducted a pooled analysis of individual patient-level data from four separate international, multicenter clinical trials. Two of these investigations were single-arm, phase 2 trials (BIRCH; data cutoff May 28, 201 and FIR; data cutoff January 7, 2015), while the other two were two-arm randomized clinical trials (phase-2 POPLAR; data cutoff May 8, 2015 and phase-3 OAK; data cutoff July 7, 2016). 

The four studies included patients with advanced NSCLC who had been previously untreated or treated with at least one line of systemic therapy, with measurable disease, good organ function, and without contraindications for chemotherapy or immune checkpoint inhibitor therapy. Data analyses were performed between February 28, 2019 and September 30, 2019.

In the POPLAR and OAK trials, control patients were treated with docetaxel once every three weeks until disease progression or unacceptable toxic effects occurred. Patients in the four trials’ experimental groups were treated with atezolizumab once every three weeks until disease progression or unacceptable toxic effects occurred.

The study’s primary outcome was the association between BMI and overall survival, progression-free survival, and treatment-related adverse events in an intention-to-treat analysis. Usable data were available for 2,110 patients from a total pool of 2,261 across the four investigations. A total of 1,434 individuals (median age 64 years; 890 men) received atezolizumab, while the remaining 676 (median age 63 years; 419 men) were treated with docetaxel. 

The study found a linear association between increasing BMI and overall survival in patients treated with atezolizumab. After adjustment for confounding variables, obesity (BMI ≥30) was found to be associated with significantly improved overall survival in patients treated with atezolizumab, but not in those who received docetaxel. 

Interestingly, the association between BMI and overall survival/progression-free survival was the strongest among patients with high programmed cell death ligand 1 (PD-L1) expression. Indeed, overall survival hazard ratios for the 436 patients with the highest category of PD-L1 expression (≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells) were 0.36 (95% CI: 0.21-0.62) for obese patients and 0.69 (95% CI: 0.48-0.98) for overweight patients. 

Similarly, hazard ratios for progression-free survival among patients with the highest category of PD-L1 were 0.68 (95% CI: 0.49-0.94) for obese patients and 0.72 (95% CI: 0.56-0.92) for overweight patients. 

Treatment-related adverse events were not associated with BMI.

“We believe we have identified for the first time that there may be a nearly linear relationship between BMI and overall survival with atezolizumab therapy when normal, overweight, and obese categories were compared,” the authors wrote. “The association between BMI and overall survival remained significant after adjustment for trial-specific stratification factors and several clinically relevant confounders.”

 

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