Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study.

Alessio Cortellini, Andrea De Giglio, Katia Cannita, Diego L. Cortinovis, Robin Cornelissen, Cinzia Baldesarri, Raffaele Giusti, Ettore D'Argento, Francesco Grossi, Matteo Santoni, Annamaria Catino, Rossana Berardi, Vincenzo Sforza, Giovanni Rossi, Lorenzo Antonuzzo, Vincenzo Di Noia, Diego Signorelli, Alain Gelibter, Mario Alberto Occhipinti, Alessandro FolladorFrancesca Rastelli, Rita Chiari, Luigi Della Gravara, Alessandro Inno, Michele De Tursi, Pietro Di Marino, Giovanni Mansueto, Federica Zoratto, Marco Filetti, Michele Montrone, Fabrizio Citarella, Maria Vittoria Pensieri, Marco Russano, Luca Cantini, Olga Nigro, Alessandro Leonetti, Paola Bordi, Gabriele Minuti, Lorenza Landi, Alessandro De Toma, Clelia Donisi, Serena Ricciardi, Maria Rita Migliorino, Valerio Maria Napoli, Gianmarco Leone, Giulio Metro, Giuseppe L. Banna, Alex Friedlaender, Alfredo Addeo, Corrado Ficorella, Giampiero Porzio

Research output: Contribution to journalArticlepeer-review


Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy.

Original languageEnglish
Pages (from-to)880-889
JournalThoracic Cancer
Issue number6
Publication statusPublished - Mar 2021


  • immunotherapy
  • non-small cell lung cancer
  • pembrolizumab
  • smoking
  • tobacco

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


Dive into the research topics of 'Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study.'. Together they form a unique fingerprint.

Cite this