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 Follador; Francesca 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

doi:10.1111/1759-7714.13852

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 journal › Article › peer-review

Abstract

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 language	English
Journal	Thoracic Cancer
DOIs	https://doi.org/10.1111/1759-7714.13852
Publication status	Accepted/In press - 2021

Keywords

immunotherapy
non-small cell lung cancer
pembrolizumab
smoking
tobacco

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine

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Cortellini, A., De Giglio, A., Cannita, K., Cortinovis, D. L., Cornelissen, R., Baldesarri, C., Giusti, R., D'Argento, E., Grossi, F., Santoni, M., Catino, A., Berardi, R., Sforza, V., Rossi, G., Antonuzzo, L., Di Noia, V., Signorelli, D., Gelibter, A., Occhipinti, M. A., ... Porzio, G. (Accepted/In press). Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study. Thoracic Cancer. https://doi.org/10.1111/1759-7714.13852

Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients : A case–control matched analysis from a large multicenter study. / Cortellini, Alessio; De Giglio, Andrea; Cannita, Katia; Cortinovis, Diego L.; Cornelissen, Robin; Baldesarri, 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.

In: Thoracic Cancer, 2021.

Research output: Contribution to journal › Article › peer-review

Cortellini, A, De Giglio, A, Cannita, K, Cortinovis, DL, Cornelissen, R, Baldesarri, C, Giusti, R, D'Argento, E , Grossi, F, Santoni, M, Catino, A, Berardi, R, Sforza, V , Rossi, G, Antonuzzo, L, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, MA, Follador, A, Rastelli, F, Chiari, R, Gravara, LD, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Pensieri, MV, Russano, M, Cantini, L, Nigro, O, Leonetti, A, Bordi, P, Minuti, G, Landi, L, De Toma, A, Donisi, C, Ricciardi, S, Migliorino, MR, Napoli, VM, Leone, G, Metro, G, Banna, GL, Friedlaender, A, Addeo, A, Ficorella, C & Porzio, G 2021, 'Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study', Thoracic Cancer. https://doi.org/10.1111/1759-7714.13852

Cortellini, Alessio ; De Giglio, Andrea ; Cannita, Katia ; Cortinovis, Diego L. ; Cornelissen, Robin ; Baldesarri, 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. / Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients : A case–control matched analysis from a large multicenter study. In: Thoracic Cancer. 2021.

@article{a7f3da8c49884501b9a97c7321c9906b,

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

abstract = "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.",

keywords = "immunotherapy, non-small cell lung cancer, pembrolizumab, smoking, tobacco",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

doi = "10.1111/1759-7714.13852",

language = "English",

journal = "Thoracic Cancer",

issn = "1759-7706",

publisher = "Blackwell Publishing Asia Pty Ltd",

}

TY - JOUR

T1 - Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients

T2 - A case–control matched analysis from a large multicenter study

AU - Cortellini, Alessio

AU - De Giglio, Andrea

AU - Cannita, Katia

AU - Cortinovis, Diego L.

AU - Cornelissen, Robin

AU - Baldesarri, Cinzia

AU - Giusti, Raffaele

AU - D'Argento, Ettore

AU - Grossi, Francesco

AU - Santoni, Matteo

AU - Catino, Annamaria

AU - Berardi, Rossana

AU - Sforza, Vincenzo

AU - Rossi, Giovanni

AU - Antonuzzo, Lorenzo

AU - Di Noia, Vincenzo

AU - Signorelli, Diego

AU - Gelibter, Alain

AU - Occhipinti, Mario Alberto

AU - Follador, Alessandro

AU - Rastelli, Francesca

AU - Chiari, Rita

AU - Gravara, Luigi Della

AU - Inno, Alessandro

AU - De Tursi, Michele

AU - Di Marino, Pietro

AU - Mansueto, Giovanni

AU - Zoratto, Federica

AU - Filetti, Marco

AU - Montrone, Michele

AU - Citarella, Fabrizio

AU - Pensieri, Maria Vittoria

AU - Russano, Marco

AU - Cantini, Luca

AU - Nigro, Olga

AU - Leonetti, Alessandro

AU - Bordi, Paola

AU - Minuti, Gabriele

AU - Landi, Lorenza

AU - De Toma, Alessandro

AU - Donisi, Clelia

AU - Ricciardi, Serena

AU - Migliorino, Maria Rita

AU - Napoli, Valerio Maria

AU - Leone, Gianmarco

AU - Metro, Giulio

AU - Banna, Giuseppe L.

AU - Friedlaender, Alex

AU - Addeo, Alfredo

AU - Ficorella, Corrado

AU - Porzio, Giampiero

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - immunotherapy

KW - non-small cell lung cancer

KW - pembrolizumab

KW - smoking

KW - tobacco

UR - http://www.scopus.com/inward/record.url?scp=85100080636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85100080636&partnerID=8YFLogxK

U2 - 10.1111/1759-7714.13852

DO - 10.1111/1759-7714.13852

M3 - Article

AN - SCOPUS:85100080636

JO - Thoracic Cancer

JF - Thoracic Cancer

SN - 1759-7706

ER -