Efficacy of immune checkpoint inhibitors in smokers vs non-smokers: A large real-world retrospective cohort analysis.

Abstract

11065 Background: Immune checkpoint inhibitors (ICIs) play a critical role in strengthening the immune response against tumors. Prior literature has shown higher objective response rates of ICIs in lung cancer patients who are smokers vs. non-smokers, thought to be due to increased expression of PD-1/PD-L1 in smokers. This study aims to assess the clinical impact of smoking on the efficacy of ICIs across multiple cancer types. Methods: This multicenter retrospective study utilized the TriNetX Network, a database containing over 130 million deidentified patient records to identify patients diagnosed with lung, breast, melanoma, colorectal, head and neck, bladder, hepatocellular, and renal cell carcinomas, who underwent subsequent treatment with ICIs (PD-1, PD-L1, and CTLA-4 inhibitors). Kaplan-Meier survival analysis was performed to assess three-year survivability. Propensity-score matching (PSM) was performed based on demographics, lab work, and pertinent comorbidities between smokers and non-smokers in each cancer type. The analysis included patients who had documented smoking status (ICD 10: Z72.0) prior to ICI therapy. Results: A total of 95,178 cancer patients receiving ICI met the inclusion criteria, of whom 15.5% were tobacco users. After PSM, 12,203 patients were in the smoking group and 12,203 were in the non-smoker group. For lung cancer patients, there was statistically significant superior survivability in the smoker group compared to the nonsmoker group, (HR: 0.894, 95% CI [0.854, 0.935]). A similar trend was identified in the colon, hepatocellular, and breast cancer groups, however, this was not statistically significant. There was no significant difference in mortality seen in the smoker versus non-smoker groups in melanoma, bladder, head and neck, and renal cell cancers. Conclusions: Our findings reaffirm previous studies demonstrating superior efficacy of ICIs in smokers with lung cancer. Additionally, this study highlights other cancer types, such as colon, hepatocellular, and breast cancers, that may exhibit improved outcomes in smokers, while also identifying cancers such as melanoma, bladder, head and neck, and renal cell carcinomas where smoking status appears to have no apparent effect on survivability. To our knowledge, this is the largest retrospective cohort study examining the impact of smoking status on ICI therapy outcomes across multiple cancer types. Survivability in smokers compared to non-smokers treated with ICIs. Cancer type (ICD 10) N (smoker) N (non-smoker) 3-year HR 95% CI Colon (C18) 292 292 0.808 (0.622,1.048) Liver (C22.0) 559 559 0.884 (0.748,1.045) Lung (C34) 8130 8130 0.894 (0.854,0.935) Breast (C50) 540 540 0.934 (0.756,1.154) Bladder (C67) 713 713 1.001 (0.856,1.169) Renal cell (C64) 706 706 1.016 (0.859,1.202) Head & neck (C76.0) 583 583 1.042 (0.888,1.224) Melanoma (C43) 680 680 1.087 (0.889,1.328)