High BMI Associated with Improved OS Following Atezolizumab in Advanced NSCLC Treatment

Higher body mass index (BMI) at baseline appeared to be independently associated with improved survival following treatment with atezolizumab (Tecentriq) in patients with advanced non-small cell lung cancer (NSCLC), according to a study published in JAMA Oncology.¹

Researchers indicated that baseline BMI should therefore be considered as a stratification factor in future immune checkpoint inhibitor therapy trials.

“This is an interesting outcome, and it raises the potential to investigate further with other cancers and other anti-cancer drugs,” lead investigator Ganessan Kichenadasse, MBBS, FRACP, medical oncology researcher at the Flinders Centre for Innovation in Cancer, said in a press release.²

Across 4 trials with a total of 2,261 patients, adequate data was available for 2,110 patients. Of that cohort, 1,434 patients received atezolizumab once every 3 weeks until disease progression or unacceptable toxic effects occurred. In total, 705 patients were normal weight, 490 were overweight, and 239 were obese among those treated with atezolizumab. The rest of the 676 patients were treated with docetaxel (Taxotere) once every 3 weeks until disease progression or unacceptable toxic effects occurred.

There was a linear correlation between increased BMI and overall survival (OS) in patients treated with atezolizumab. Obesity (BMI ≥ 30 [calculated as weight in kilograms divided by height in meters squared]) was associated with significantly improved OS in those treated with atezolizumab, but not in patients who received docetaxel after adjusting for confounding variables. The association between BMI and OS/progression-free survival (PFS) was the greatest in the high PD-L1 expression subgroup.

Overall survival for patients with the highest category of PD-L1 expression (≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells; n = 436) had hazard ratios (HRs) of 0.36 (95% CI, 0.21-0.62) for the group with obesity and 0.69 (95% CI, 0.48-0.98) for the group with overweight. Patients with the highest category of PD-L1 expression had PFS HRs of 0.68 (95% CI, 0.49-0.94) for the group with obesity and 0.72 (95% CI, 0.56-0.92) for the group with overweight. Treatment-related adverse events were not associated with BMI. 

“Our study provides new evidence to support the hypothesis that high BMI and obesity may be associated with response to immunotherapy,” Kichenadasse said. 

The association between obesity and cancer diagnosis is complex, given that although obesity increases the risk of developing certain cancer types, such as breast cancers, obesity guards against worse outcomes in patients with advanced cancers, such as lung cancers that are correlated with wasting. This association to improved survival in patients with lung cancer may not be specific to immune checkpoint inhibitor therapy, however. Previous research and data from this study, in conjunction, suggest that obesity probably has a varying influence across the gamut of treatment interventions for lung cancer. 

Additionally, given that men and women have different body compositions, there is a varying prevalence of obesity between the sexes. However, the interaction between sex and immune checkpoint inhibitor therapy outcomes is uncertain. Contrary to prior reports, the data reported in this study indicated that sex had no significant effect on the improved survival seen in men and women with obesity.

Future research is necessary to provide further understanding of BMI subroups according to the researchers.

References:

1. Kichenadasse G, Miners JO, Mangoni AA, Rowland A, Hopkins AM, Sorich MJ. Association Between Body Mass Index and Overall Survival With Immune Checkpoint Inhibitor Therapy for Advanced Non-Small Cell Lung Cancer. JAMA Oncology. doi:10.1001/jamaoncol.2019.5241.

2. High BMI may improve cancer survival [news release]. Adelaide, South Australia. Published December 26, 2019. eurekalert.org/pub_releases/2019-12/fu-hbm122219.php. Accessed January 17, 2020.