Obesity, Weight Loss Linked to Lung Cancer Immunotherapy Outcomes

Baseline body mass index (BMI) and weight loss during treatment with the programmed death 1 (PD-1)–targeting immune checkpoint inhibitors nivolumab and pembrolizumab appear to be associated with survival outcomes, according to a retrospective analysis of real-world clinical data from patients with metastatic non–small-cell lung cancer (NSCLC; abstract 6553) that was presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

“Obese baseline BMI is associated with longer overall survival while an underweight baseline BMI is associated with decreased survival,” said lead author Jizu Zhi, PhD, of the US Food and Drug Administration in Silver Spring, Maryland, and coauthors.

Regardless of patients’ baseline BMI, weight loss (including declines in BMI as small as 5%) was associated with poorer survival (P < .0001), the researchers reported in a poster presentation.

“Patients with an underweight BMI at the start of PD-1 therapy are more likely to be younger, female, and have nonsquamous histology,” the authors noted. “Men were more likely than women to be obese or overweight at the start of PD-1 therapy.”

Metastatic NSCLC is the single leading cause of cancer deaths in the United States. Poor performance status is prognostic but is frequently missing from patients’ electronic health records. In contrast, weight and height, which can be used to calculate BMI, are almost always available in patient records, and BMI over time might serve as an indirect measure for cachexia and performance status.

“We hypothesized that lower baseline BMI and decreased BMI over time may serve as a proxy for deteriorated real-world performance status and can be prognostic for metastatic NSCLC patients treated with PD-1 therapy,” Zhi and coauthors reported.

They conducted their analysis of medical records for 1,034 patients with metastatic NSCLC who were seen at least twice between 2011 and 2016 and who underwent immune checkpoint blockade with nivolumab or pembrolizumab. A total of 69 patients were underweight at baseline, 488 had normal BMI, 307 were overweight, and 170 were obese.

“At 90 days [from immunotherapy initiation], the trend for an association between a decrease in BMI > 5% and overall survival continues in patients overall and for each baseline BMI category,” they reported.

The line of therapy in which immune checkpoint blockade was initiated did not affect overall survival. But survival bias might represent a confounding factor and the study’s small sample size might have amplified the impact of missing data, the researchers cautioned.

Validation of these findings with a larger cohort is needed to clarify the nature of the association between BMI and survival outcomes among patients on immunotherapy for metastatic NSCLC.