Clinical Study Investigates 'Obesity Paradox' in Treatment of Non-Small Cell Lung Cancer

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New clinical data published by JAMA Network Open indicates that immune checkpoint inhibitor (ICI) therapy may not be the optimal first-line treatment for patients with advanced non–small cell lung cancer (aNSCLC) and with overweight or obesity.¹ Interestingly, the study showed that among patients with aNSCLC treated with ICI or conventional chemotherapy, overweight or obesity was linked to a lesser risk of mortality than a lower body mass index (BMI).

“This cohort study showed a lack of association between immunotherapy and improved survival in patients with aNSCLC and overweight or obesity compared with conventional chemotherapy,” the study authors wrote. “This finding supports the possibility that patients with obesity may have an inadequate response to immunotherapy. This suggests that ICI therapy may not necessarily be the optimal first-line therapy for patients with overweight or obesity, and the use of conventional chemotherapy should also be considered.”¹

The vast majority of lung cancer cases are NSCLC, most of which are unresectable or metastatic at diagnosis, highlighting the need for strong treatment options. Targeted therapies and ICIs have improved survival rates for the disease; however, lung cancer remains the leading cause of cancer deaths in the United States. Common treatments for metastatic NSCLC include chemotherapy, immunotherapy, chemoimmunotherapy, and targeted therapies. ICIs are typically used to treat metastatic NSCLC, including in the front-line setting.²

“Patients with cancer and obesity are generally recognized to have a less-favorable prognosis than their counterparts who have a normal weight,” the study authors wrote. “Therefore, both the American Cancer Society and the European Society for Medical Oncology advocate implementing weight management strategies among cancer survivors. However, several observational studies have reported that patients with cancer and a higher (BMI) experience improved survival compared with patients with normal weight and cancer receiving chemotherapy. This discrepancy is known as the obesity paradox and exists not only in patients with cancer receiving conventional chemotherapy, but also in those undergoing treatment with (ICIs).”¹

The study authors noted that preclinical research shows obesity inhibits the response to treatment with anti–PD-1 therapy. To further investigate this obesity paradox, the study authors analyzed whether BMI affects the association of first-line immunotherapy on OS in patients with aNSCLC compared to conventional chemotherapy, as well as the potential for inadequate treatment responses to ICI compared to conventional chemotherapy in patients with obesity and aNSCLC.

Investigators evaluated administrative claims data from advanced treatment centers in Japan between December 1, 2015, and January 31, 2023. Participants were aged 18 years or above with aNSCLC and who were treated with ICI treatment or conventional chemotherapy. Investigators identified 31,257 patients with aNSCLC, of whom 12,816 patients were administered ICI therapy (mean [SD] age, 70.2 [9.1] years; 10 287 [80.3%] men) and 18,441 were administered conventional chemotherapy (mean [SD] age, 70.2 [8.9] years; 14 139 [76.7%] men).

The data show that compared to conventional chemotherapy, ICI therapy was linked to a significantly reduced hazard of mortality (eg, BMI 24: hazard ratio [HR], 0.81; 95% CI, 0.75-0.87) in patients with BMI less than 28. This association was not observed among those with a BMI of 28 or more (eg, BMI 28: HR, 0.90; 95% CI, 0.81-1.00), however.

“The reason why patients with aNSCLC who received ICI therapy or conventional chemotherapy exhibited an association between a decreased hazard of mortality and increasing BMI is unclear. This association was observed with conventional chemotherapy irrespective of age and sex, suggesting potential stability compared with ICI therapy. Further studies are needed to determine which patient characteristics would increase efficacy in patients with obesity,” the study authors concluded.¹

References

1. Ihara Y, Sawa K, Imai T, et al. Immunotherapy and Overall Survival Among Patients With Advanced Non–Small Cell Lung Cancer and Obesity. JAMA Netw Open. 2024;7(8):e2425363. doi:10.1001/jamanetworkopen.2024.25363

2. Schepers A, McPherson J, Mohs J. Exploring the New Standard of Care for the Frontline Treatment of Non–Small Cell Lung Cancer. Presented at American Society of Health-System Pharmacists 2022 Midyear Clinical Meeting.