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

Thoracic Cancer

Pietro Di Marino¹  Ettore D'Argento²  Corrado Ficorella³  Diego Signorelli⁴  Alessandro De Toma⁴  Giulio Metro⁵  Michele De Tursi⁶  Lorenzo Antonuzzo⁷  Alessandro Follador⁸  Gianmarco Leone⁹  Valerio Maria Napoli⁹  Gabriele Minuti^1,10  Cinzia Baldessari^1,11  Luca Cantini^1,12  Robin Cornelissen^1,12  Alessio Cortellini^1,13  Maria Vittoria Pensieri^1,13  Lorenza Landi^1,14  Andrea De Giglio^1,14  Giovanni Rossi^1,15  Alain Gelibter^1,16  Mario Alberto Occhipinti^1,16  Olga Nigro^1,17  Marco Russano^1,18  Fabrizio Citarella^1,18  Giovanni Mansueto^1,19  Francesca Rastelli^2,20  Matteo Santoni^2,21  Diego L. Cortinovis^2,22  Rita Chiari^2,23  Federica Zoratto^2,24  Raffaele Giusti^2,25  Marco Filetti^2,25  Katia Cannita^2,26  Giampiero Porzio^2,26  Francesco Grossi^2,27  Clelia Donisi^2,28  Paola Bordi^2,29  Alessandro Leonetti^2,29  Rossana Berardi^3,30  Giuseppe L. Banna^3,31  Alfredo Addeo^3,32  Alex Friedlaender^3,32  Alessandro Inno^3,33  Luigi Della Gravara^3,34  Maria Rita Migliorino^3,35  Serena Ricciardi^3,35  Vincenzo Sforza^3,36  Michele Montrone^3,37  Annamaria Catino^3,37  Vincenzo Di Noia^3,38 

[1] Clinical Oncology Unit S.S. Annunziata Hospital Chieti Italy;Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS Rome Italy;Department of Biotechnology and Applied Clinical Sciences University of L'Aquila L'Aquila Italy;Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy;Department of Medical Oncology Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia Perugia Italy;Department of Medical, Oral & Biotechnological Sciences University G. D'Annunzio, Chieti‐Pescara Chieti Italy;Department of Oncology Careggi University Hospital Florence Italy;Department of Oncology University Hospital Santa Maria Della Misericordia Udine Italy;Department of Oncology University of Turin, San Luigi Hospital Orbassano Italy;Department of Oncology and Hematology AUSL Romagna Ravenna Italy;Department of Oncology and Hematology Modena University Hospital Modena Italy;Department of Pulmonary Diseases Erasmus Medical Center Rotterdam The Netherlands;Department of Surgery and Cancer Imperial College London London United Kingdom;Division of Medical Oncology, S.Orsola‐Malpighi Hospital University of Bologna Bologna Italy;Lung Cancer Unit IRCCS Ospedale Policlinico San Martino Genoa Italy;Medical Oncology (B) Policlinico Umberto I, "Sapienza" University of Rome Rome Italy;Medical Oncology ASST‐Sette Laghi Varese Italy;Medical Oncology Campus Bio‐Medico University Rome Italy;Medical Oncology F. Spaziani Hospital Frosinone Italy;Medical Oncology Fermo Area Vasta 4 Fermo Italy;Medical Oncology Hospital of Macerata Macerata Italy;Medical Oncology Ospedale San Gerardo Monza Italy;Medical Oncology Ospedali Riuniti Padova Sud "Madre Teresa Di Calcutta" Monselice Italy;Medical Oncology Santa Maria Goretti Hospital Latina Italy;Medical Oncology St. Andrea Hospital Rome Italy;Medical Oncology St. Salvatore Hospital L'Aquila Italy;Medical Oncology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy;Medical Oncology Unit University Hospital and University of Cagliari Cagliari Italy;Medical Oncology Unit University Hospital of Parma Parma Italy;Oncology Clinic Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona Ancona Italy;Oncology Department Queen Alexandra University Hospital, Portsmouth Hospitals NHS Trust Portsmouth UK;Oncology Department University Hospital of Geneva Geneva Switzerland;Oncology Unit IRCCS Ospedale Sacro Cuore Don Calabria Negrar Italy;Pneumo‐Oncology Unit Monaldi Hospital Naples Italy;Pneumo‐Oncology Unit St. Camillo‐Forlanini Hospital Rome Italy;Thoracic Medical Oncology Istituto Nazionale Tumori 'Fondazione G Pascale', IRCCS Naples Italy;Thoracic Oncology Unit Clinical Cancer Center IRCCS Istituto Tumori "Giovanni Paolo II" Bari Italy;Unità di Oncologia medica e Terapia Biomolecolare, Azienda Ospedaliero‐Universitaria Ospedali Riuniti di Foggia Foggia Italy;

关键词: immunotherapy;    non‐small cell lung cancer;    pembrolizumab;    smoking;    tobacco;   

DOI  :  10.1111/1759-7714.13852

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown