Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis

Smoking may influence cancer treatment outcomes; however, there is conflicting evidence on the efficacy of immune checkpoint inhibitors (ICIs) in active smokers. It has been suggested that smokers receiving ICIs may achieve improved outcomes compared with non‑smokers. The present study aimed to challenge this assumption by investigating the prognostic impact of smoking status and other characteristics in patients with metastatic or advanced cancer undergoing ICI therapy. In the present study, patients with predetermined solid tumors who received ICIs either as a monotherapy or in combination regimens in a palliative treatment setting were retrospectively evaluated. Patients were included if they had received >1 dose of an ICI and had an available smoking status. Kaplan‑Meier estimates were used to analyze the associations between smoking status and overall survival (OS) and progression‑free survival (PFS). The patient baseline characteristics were assessed as potential prognostic markers using univariate and multivariate analyses. Of the 464 patients evaluated, 180 met the inclusion criteria. The cohort included patients with lung cancer (n=94), renal cell carcinoma (n=18), urothelial cancer (n=21), melanoma (n=3), and head and neck cancer (n=44). The median OS and PFS times for the whole cohort were 39.1 and 5.5 months, respectively. Patients were categorized as never‑smokers (n=45, 25%), former smokers (n=81, 45%) and active smokers (n=54, 30%). The median OS times for the never, former and active smokers were 66.4, 31.6 and 13.9 months, respectively. When comparing the active smokers with the former and never smokers, the median OS times were 13.9 vs. 41.1 months (P=0.069, trend). Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) performance status ≥3 [hazard ratio (HR), 5.85; P=0.002], neutrophil‑to‑lymphocyte ratio (NLR; HR, 1.11; P=0.017), lactate dehydrogenase (LDH; HR, 1.00; P<0.001) and C‑reactive protein (CRP) levels as continuous variables (HR, 1.01; P=0.002) as significant predictors of a poorer OS. For PFS, multivariate analysis identified sex (HR, 0.69; P=0.049), age (HR, 0.98; P=0.014) and ECOG performance status ≥3 (HR, 5.83; P<0.001) as independent predictors of a shorter PFS. In conclusion, contrary to prior hypotheses suggesting improved outcomes for smokers undergoing ICI therapy, the results of the present study demonstrated a trend towards impaired survival outcomes in active smokers compared with never and former smokers. The independent prognostic factors for a poorer OS included a poor ECOG performance status, CRP level, LDH level and NLR.