Summary: Those with a higher body mass index who are given atezolizumab to treat cancer have an improved rate of survival, a new study reveals.
Source: Flinders University
Above average or high BMI – often linked to cancers, diabetes, cardiovascular and other diseases – may in some cases improve the chance of survival among certain cancers, new research from Flinders University indicates.
Focusing on clinical trials of atezolizumab, a common immunotherapy treatment for non-small-cell lung cancer (NSCLC), the Australian cancer researchers found improved responsiveness to the drug in those with a high body mass index (BMI).
The surprising result – published today in JAMA Oncology – contrast with regular warnings about the health risks of patients who are overweight and obese.
“This is an interesting outcome and it raises the potential to investigate further with other cancers and other anti-cancer drugs,” says lead investigator Dr Ganessan Kichenadasse, a medical oncology researcher at the Flinders Centre for Innovation in Cancer.
“We need to do further studies into the possible link between BMI and related inflammation, which might help to understand the mechanisms behind paradoxical response to this form of cancer treatment.”
“Previous studies have explored a concept called as ‘obesity paradox’ where obesity is associated with increased risks for developing certain cancers and, counter-intuitively, may protect and give greater survival benefits in certain individuals.
“Our study provides new evidence to support the hypothesis that high BMI and obesity may be associated with response to immunotherapy,” says Dr Kichenadasse.
The Flinders researchers found NSCLC patients with high BMI (BMI ? 25 kg/m2) in four clinical trials had a significant reduction in mortality with atezolizumab, apparently benefiting from immune checkpoint inhibitor (ICI) therapy.
Treatment options for this form of lung cancer are rapidly evolving and includes ICIs, molecular targeted drugs and chemotherapies.
“While our study only looked at baseline and during treatment, we believe it warrants more studies into the potentially protective role of high BMI in other cancer treatments.”
The WHO estimates at least 2.8 million people die each year as a result of being overweight or obese. Overweight and obesity leads to adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. Risks of coronary heart disease, ischemic stroke and type 2 diabetes mellitus increase steadily with increasing body mass index (BMI), a measure of weight relative to height.
Of the 1434 participants studied in the Australian research, 49% were normal weight, 34% were overweight and 7% were obese.
Funding: The research was part funded by Cancer Council of South Australia.
Ganessan Kichenadasse – Flinders University
The image is in the public domain.
Original Research: Closed access
“Association between body mass index (BMI) and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer: analysis of atezolizumab clinical trials”. Ganessan Kichenadasse, FRACP; John O. Miners, PhD; Arduino A. Mangoni, PhD; Andrew Rowland, PhD; Ashley M. Hopkins, PhD; Michael J. Sorich, PhD.
JAMA Oncology doi:10.1001/jamaoncol.2019.5241.
Association between body mass index (BMI) and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer: analysis of atezolizumab clinical trials
High body mass index (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 non–small cell lung cancer treated with atezolizumab remains unknown.
To examine whether BMI is associated with survival outcomes and adverse events in patients with non–small cell lung cancer (NSCLC) treated with atezolizumab.
Design, Setting, and Participants
A pooled analysis of individual patient-level data from 4 international, multicenter clinical trials was performed. Two were single-arm phase 2 trials (BIRCH [data cutoff of May 28, 2015] and FIR [data cutoff of January 7, 2015]), and 2 were 2-arm randomized clinical trials (POPLAR [phase 2; data cutoff of May 8, 2015] and OAK [phase 3; data cutoff of July 7, 2016]). Patients with advanced NSCLC previously untreated or treated with at least 1 line of systemic therapy, with measurable disease and good organ function and without contraindications for chemotherapy or immune checkpoint inhibitor therapy, were included in these trials. Data analyses were performed from February 28, 2019, to September 30, 2019.
The control group was treated with docetaxel once every 3 weeks until disease progression or unacceptable toxic effects occurred in POPLAR and OAK. The experimental group was treated with atezolizumab once every 3 weeks until disease progression or unacceptable toxic effects occurred in all available trials.
Main Outcomes and Measures
Association between BMI and overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Intention-to-treat analysis was conducted.
Adequate data were available for 2110 patients from a total pool of 2261 across 4 trials. Of those 2110, 1434 patients (median age, 64 years [range, 57-70 years]; 890 men [62%]) received atezolizumab and 676 patients (median age, 63 years[range, 57-69 years]; 419 men [62%]) received docetaxel. There was a linear association between increasing BMI and 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 patients treated with atezolizumab, but not in those who received docetaxel after adjusting for confounding variables. The association between BMI and OS/PFS was the strongest 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 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 hazard ratios 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.
Conclusions and Relevance
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.