Immunotherapy and Survival in NSCLC: Does Obesity Matter?

TOPLINE:

Among patients with overweight or obesity, frontline immunotherapy for advanced non–small cell lung cancer (NSCLC) was not associated with a survival benefit compared with conventional chemotherapy. Overall, however, compared with low body mass index (BMI), overweight or obesity was associated with a lower risk for mortality among patients receiving either therapy.

METHODOLOGY:

• The association between BMI and overall survival in patients with cancer who receive immunotherapy or conventional chemotherapy in the frontline remains unclear. Patients with cancer and obesity are generally considered to have a worse prognosis, but some data suggest an obesity paradox, where patients with cancer and a higher BMI demonstrate better overall survival following immunotherapy or chemotherapy.
• To clarify whether (or how) BMI affects overall survival outcomes and the optimal frontline treatment choice, researchers evaluated 31,257 patients with advanced NSCLC from Japan who received immune checkpoint inhibitors (n = 12,816) or conventional chemotherapy (n = 18,441).
• Patient outcomes were assessed according to weight categories and frontline therapy type (immune checkpoint inhibitors or conventional chemotherapy), with overall survival as the primary outcome.
• A BMI < 18.5 kg/m² was considered underweight, 18.5-24.9 kg/m² was considered normal weight, 25.0-29.9 kg/m² was considered overweight, and ≥ 30.0 kg/m² was considered obese.

TAKEAWAY:

• In the overall population, regardless of weight, patients who received chemotherapy had a higher mortality rate than those who received immunotherapy — 35.9% vs 28.0%, respectively — over a follow-up of 3 years.
• However, overweight or obesity was associated with a lower risk for mortality compared with a lower BMI among patients with advanced NSCLC, regardless of whether they received immune checkpoint inhibitor therapy or conventional chemotherapy.
• Among patients who received immunotherapy, the risk for mortality decreased steadily as BMI increased from 15 to 24 kg/m² and then increased at higher BMIs, indicating a U-shaped association.
• Immunotherapy was associated with a significant improvement in overall survival compared with conventional chemotherapy among patients with a BMI < 28; however, researchers observed no difference in overall survival between the two therapies in those with a BMI ≥ 28.

IN PRACTICE:

Overall, “these results support the presence of the obesity paradox in patients with [advanced] NSCLC who underwent either therapy,” the authors concluded.

But when focused on patients in the higher BMI group, there was no overall survival benefit with the frontline immunotherapy vs the conventional chemotherapy. “Immunotherapy therapy may not necessarily be the optimal first-line therapy for patients with overweight or obesity,” the authors wrote, adding that “the use of conventional chemotherapy should also be considered.”

SOURCE:

The study, led by Yasutaka Ihara, PharmD, Osaka Metropolitan University, Osaka, Japan, was published online on August 2 in JAMA Network Open.

LIMITATIONS: 

Retrospective design has inherent bias. PD-L1 status was not known, and the inclusion of Japanese population may have limited the generalizability of the findings. 

DISCLOSURES:

This study received funding from the Graduate School of Medicine, Osaka Metropolitan University. Several authors reported receiving personal fees from various pharmaceutical sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.