Smokers with PD-L1 Positive Status Benefit More than Non-Smokers in All Types of Cancer When Treated by Anti- PD-1 and PD-L1 Drugs

Abstract

Background: There are potential benefits for cancer patients with programmed death-1 (PD-1) positive status to have a smoking status when treated with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-1/PD-L1) inhibitors. This study is to compare the advantage of smokers with PD-L1 positive status over that of non-smokers in all types of cancer when treated by Anti-PD-1 and PD-L1 drugs. Methods: This study is a prospectively planned meta-analysis of Hazard ratios (HR) of both progression-free survival (PFS) and overall survival (OS) from the randomized clinical trials enrolling at least 100 participants treated with cancer drugs in different smoking status. HR of both PFS and OS were independently screened, extracted and compared among patients with different smoking behavior status from: 1) ten clinical trials of PD-1/PD-L1 inhibitors for non-small cell lung cancer (NSCLC), 2) Thirty-nine large clinical trials of all known other cancer drugs for NSCLC, 3) six trials of patients with on other types of cancer treated with PD-1/PD-L1 inhibitors, and 4) four trials of patients with other types of cancer treated with other drugs. HR values from smokers and non-smokers were used as the criteria of response to drug treatment and were compared with T-tests and Meta-analysis. Findings: The primary outcome was smokers who were treated with PD-1/PD-L1 inhibitors had better outcomes than non-smokers when the drug was used as monotherapy in the treatment of NSCLC as well as other types of cancer. A total of 59 clinical trials with more than 40,000 total patients were included in this systematic review and 27,600 in meta-analysis. Among NSCLC patients, treated with PD-1/PD-L1 inhibitors, smokers had a better outcome with a mean HR value of 0.070 lower than non-smokers when the drugs were used as monotherapy. Among patients having other types of cancer, response to PD-1/PD-L1 inhibitor treatment was better in smokers than non-smokers, with a mean HR value of 0.028-0.038 in smokers less than the non-smokers . Response in smokers was worse than non-smokers among cancer patients treated with all other known drugs. Interpretation: For all types of cancer patients with PD-L1 positive status, smoking appears to confer some benefit to patients treated with PD-1/PD-L1 inhibitors. Funding Statement: This work was partially supported by funding from merit grant I01 BX000671 to WG from the Department of Veterans Affairs and the Veterans Administration Medical Center in Memphis, TN, USA and University of Tennessee Health Science Center, TN, USA. Declaration of Interests: Authors have no interest of conflict.