Association between Smoking and Survival Benefit of Immunotherapy in Advanced Malignancies: A Systematic Review and Meta-Analysis

Christopher J.D. Wallis, Raj Satkunasivam, Mohit Butaney, Usman A. Khan, Hanan A. Goldberg, Stephen J. Freedland, Sandip P. Patel, Omid Hamid, Sumanta K. Pal, Zachary Klaassen

Research output: Contribution to journalArticle


Objectives:Smoking is associated with an increased tumor mutational burden. As tumor mutational burden has been shown to correlate with response to immunotherapy (IO), we hypothesized that a history of smoking may be associated with better response to IO.Methods:We utilized a systematic review with stratified meta-analysis of randomized clinical trials of IO versus standard of care in patients with advanced solid organ malignancies.Results:Among 9 relevant studies, we found no significant difference in the benefit of IO, compared with other systemic therapies, between ever smokers (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.58-1.04; P=0.09) and never smokers (HR, 0.75; 95% CI, 0.67-0.86; P<0.0001) (test for difference P=0.83). We also observed no significant difference between current (HR, 0.92; 95% CI, 0.63-1.34; P=0.66; I2=67%) and never smokers (HR, 0.74; 95% CI, 0.59-0.93; P=0.01; I2=46%) (test for difference P=0.35).Conclusions:Stratified meta-analysis demonstrates that smoking status is not significantly associated with the response to IO in the treatment of advanced solid organ malignancies.

Original languageEnglish (US)
Pages (from-to)711-716
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Issue number9
StatePublished - Sep 1 2019



  • immunotherapy
  • smoking
  • tumor burden

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this