A retrospective study evaluating clinical predictors of duration of response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

Abstract

e20665 Background: Immune Checkpoint Inhibitors (ICI) with/without chemotherapy has become the standard of care for the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). Similar to the response rate, durability of response to ICI is quite variable. While programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) have been described to predict response to ICI, little is known about the clinical predictors of duration of response (DoR). Methods: A retrospective chart review of patients (pts) with advanced NSCLC treated with ICI based therapy at Karmanos Cancer Institute was conducted. Data were collected on demographics, clinical characteristics, and tumor characteristics. Univariable and multivariable cox regression analyses were performed for six pre-chosen covariates (histology, prior radiation therapy, brain metastasis, occurrence of immune-related adverse events (irAEs), statin use and smoking status) to see the associations with the DoR to ICI. Results: One hundred thirty-one pts were included in the analysis (68% adenocarcinoma, 60% received prior radiation, 20% had brain metastasis, 26% developed irAEs, 33% were on a statin, 69% former smokers, 12% current smokers and 19% never smokers). Overall median DoR was 149 days (range, 14-1934 days). On multivariable analysis, longer DoR to ICI was observed in pts with non-adenocarcinoma histology (HR: 0.65; p = 0.050; CI: 0.42-1.00, median DoR 242.5 days) and current smokers (HR: 0.53; p = 0.031; CI: 0.30-0.95, median DoR 206.5 days). Other variables, including the presence of brain metastasis, prior radiation therapy, occurrence of irAEs and statin use had no significant relationship with the DoR. Conclusions: Tumor histology and smoking status were statistically and clinically significant predictors of durability of response to ICI in advanced NSCLC, presumably secondary to higher tumor mutational burden. Presence of brain metastasis did not adversely impact DoR to ICI.