Naveed Saleh, MD, MS, for MDLinx | April 15, 2019
Muscle loss, or sarcopenia, predicts worse outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with programmed cell death protein-1 (PD-1) blockade, according to the results of a study recently published in Scientific Reports.
“Sarcopenia is a well-known risk factor associated with poor outcomes for several cancer types,” said lead author of the study, Takayuki Shiroyama, MD, Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan. “Because muscle degradation is associated with a dysregulated immune response, we wanted to investigate how, in lung cancer patients, sarcopenia impacts the efficacy of PD-1 inhibitor therapy.”
In this preliminary retrospective study, Dr. Shiroyama et al evaluated sarcopenia via computed tomography (CT) in 42 Asian subjects using psoas muscle index (PMI) cut-off values. These subjects were treated with PD-1 inhibitors nivolumab or pembrolizumab for previously treated advanced NSCLC. In total, 52.4% of subjects had sarcopenia.
Sarcopenia was correlated with poorer progression-free survival (PFS) compared with that of patients without sarcopenia (median: 2.1 vs 6.8 months; P=0.004). Furthermore, compared with subjects with sarcopenia, those without the disease exhibited a higher overall response rate to treatment with PD-1 inhibitors (40.0% vs 9.1%; P=0.025) and 1-year PFS rate (38.1% vs 10.1%).
The investigators noticed certain trends in the study. For instance, there was no significant difference in PFS among underweight, normal weight, and overweight subjects.
Upon univariate analysis, factors significantly tied to poorer PFS included male sex, Eastern Cooperative Oncology Group performance status ≥ 2, and sarcopenia.
After controlling for sex and performance status, the hazard ratio of sarcopenia for PFS was 2.18 (95% confidence interval: 0.92–5.17; P=0.077).
To date, several biomarkers have been used with immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and tumor mutation burden. But these markers are lacking when used alone. Additional biomarkers that are easy to measure, such as PMI, may complement current biomarkers. These additional biomarkers may help identify patients who will sustain a durable response to PD-1 inhibitor therapy.
PMI entails measuring the cross-sectional area of skeletal muscles using abdominal CT at the level of the third lumbar vertebra (L3). It is a widely used method to identify and confirm sarcopenia diagnosis. Furthermore, the PMI at the level of L3 serves as proxy skeletal muscle mass.
“Our findings suggest that baseline skeletal muscle mass has a substantial impact on PD-1 inhibitor efficacy,” stated Dr. Shiroyama. “As such, skeletal muscle mass might be useful for predicting whether treatment is likely to be effective.”
Finally, the researchers suggested that new drugs that increase muscle mass may be extremely important for patients with cancer. These patients may attain optimal long-term treatment outcomes from PD-1-inhibitor therapy by boosting muscle mass.