Tobacco smoking and cessation and PD-L1 inhibitors in non-small cell lung cancer (NSCLC): a review of the literature

BACKGROUND: Programmed death ligand 1 (PD-L1) targeting immunotherapies, as pembrolizumab and nivolumab, have significantly improved outcome in patients with non-small cell lung cancer (NSCLC). Tobacco smoking is the number one risk factor for lung cancer and is linked to 80%–90% of these cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcome. We aimed to review the knowledge in immunotherapy. PATIENTS AND METHODS: A systematic review was done. We searched for documents and articles published in English language and registered in Cochrane Library, National Health Service (NHS) Centre for Reviews and Dissemination (CRD), Embase or Medline. The search terms were (A) (Lung cancer or NSCLC) with (pembrolizumab or nivolumab) with PD-L1 with (tobacco or smoking) and (B) Lung Neoplasms and Immunotherapy and (smoking cessation or patient compliance). 68 papers were detected and two more were added during review process (references) and six based on information from the manufacturers. RESULTS: Nine papers were selected. High PD-L1 expression (≥50%) was correlated with current/ever smoking history in three studies. Six studies revealed a higher overall response rate (ORR) among current/former smokers. The ORR was generally (six studies) better among the current/former smoker group. So also when tumours had a molecular ‘smoking signature’ (one study). This was probably due to a higher mutational burden. In two studies, minor or no difference was revealed. One study (KEYNOTE-024) compared former and current smokers, and documented pembrolizumab being more effective among former smokers than current smokers. CONCLUSIONS: Tobacco smoking patients with NSCLC generally have a higher PD-L1 tumour proportion score and experience a better ORR of immunotherapy than no smokers. There is little evidence on the effect of smoking during immunotherapy, but one study (KEYNOTE-024) may indicate survival gains of smoking cessation.