Smoking status during first‐line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study
Authors: Cortellini Alessio , De Giglio Andrea , Cannita Katia , Cortinovis Diego L. , Cornelissen Robin , Baldessari Cinzia , Giusti Raffaele , D'Argento Ettore , Grossi Francesco , Santoni Matteo , Catino Annamaria , Berardi Rossana , Sforza Vincenzo , Rossi Giovanni , Antonuzzo Lorenzo , Di Noia Vincenzo , Signorelli Diego , Gelibter Alain , Occhipinti Mario Alberto , Follador Alessandro , Rastelli Francesca , Chiari Rita , Gravara Luigi Della , Inno Alessandro , De Tursi Michele , Di Marino Pietro , Mansueto Giovanni , Zoratto Federica , Filetti Marco , Montrone Michele , Citarella Fabrizio , Pensieri Maria Vittoria , Russano Marco , Cantini Luca , Nigro Olga , Leonetti Alessandro , Bordi Paola , Minuti Gabriele , Landi Lorenza , De Toma Alessandro , Donisi Clelia , Ricciardi Serena , Migliorino Maria Rita , Napoli Valerio Maria , Leone Gianmarco , Metro Giulio , Banna Giuseppe L. , Friedlaender Alex , Addeo Alfredo , Ficorella Corrado , Porzio Giampiero 
Published: February 2021

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.