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

被引：44

作者：

Cortellini, Alessio ^{[1
,2
]}

De Giglio, Andrea ^{[3
]}

Cannita, Katia ^{[4
]}

Cortinovis, Diego L. ^{[5
]}

Cornelissen, Robin ^{[6
]}

Baldesarri, Cinzia ^{[7
]}

Giusti, Raffaele ^{[8
]}

D'Argento, Ettore ^{[9
]}

Grossi, Francesco ^{[10
]}

Santoni, Matteo ^{[11
]}

Catino, Annamaria ^{[12
]}

Berardi, Rossana ^{[13
]}

Sforza, Vincenzo ^{[14
]}

Rossi, Giovanni ^{[15
]}

Antonuzzo, Lorenzo ^{[16
]}

Di Noia, Vincenzo ^{[17
]}

Signorelli, Diego ^{[18
]}

Gelibter, Alain ^{[19
]}

Occhipinti, Mario Alberto ^{[19
]}

Follador, Alessandro ^{[20
]}

Rastelli, Francesca ^{[21
]}

Chiari, Rita ^{[22
]}

Gravara, Luigi Della ^{[23
]}

Inno, Alessandro ^{[24
]}

De Tursi, Michele ^{[25
]}

Di Marino, Pietro ^{[26
]}

Mansueto, Giovanni ^{[27
]}

Zoratto, Federica ^{[28
]}

Filetti, Marco ^{[8
]}

Montrone, Michele ^{[12
]}

Citarella, Fabrizio ^{[29
]}

Pensieri, Maria Vittoria ^{[1
,2
]}

Russano, Marco ^{[29
]}

Cantini, Luca ^{[6
,13
]}

Nigro, Olga ^{[30
]}

Leonetti, Alessandro ^{[31
]}

Bordi, Paola ^{[31
]}

Minuti, Gabriele ^{[32
]}

Landi, Lorenza ^{[3
]}

De Toma, Alessandro ^{[18
]}

Donisi, Clelia ^{[33
,34
]}

Ricciardi, Serena ^{[35
]}

Migliorino, Maria Rita ^{[35
]}

Napoli, Valerio Maria ^{[36
]}

Leone, Gianmarco ^{[36
]}

Metro, Giulio ^{[37
]}

Banna, Giuseppe L. ^{[38
]}

Friedlaender, Alex ^{[39
]}

Addeo, Alfredo ^{[39
]}

Ficorella, Corrado ^{[2
,4
]}

机构：

[1] Imperial Coll London, Dept Surg & Canc, London, England

[2] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy

[3] Univ Bologna, S Orsola Malpighi Hosp, Div Med Oncol, Bologna, Italy

[4] St Salvatore Hosp, Med Oncol, Laquila, Italy

[5] Osped San Gerardo, Med Oncol, Monza, Italy

[6] Erasmus MC, Dept Pulm Dis, Rotterdam, Netherlands

[7] Modena Univ Hosp, Dept Oncol & Hematol, Modena, Italy

[8] St Andrea Hosp, Med Oncol, Rome, Italy

[9] Fdn Policlin A Univ A Gemelli IRCCS, Comprehens Canc Ctr, Rome, Italy

[10] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Med Oncol Unit, Milan, Italy

[11] Hosp Macerata, Med Oncol, Macerata, Italy

[12] IRCCS Ist Tumori Giovanni Paolo II, Thorac Oncol Unit, Clin Canc Ctr, Bari, Italy

[13] Univ Politecn Marche, Osped Riuniti Ancona, Oncol Clin, Ancona, Italy

[14] IRCCS, Thorac Med Oncol, Ist Nazl Tumori Fdnd G Pascale, Naples, Italy

[15] IRCCS Osped Policlin San Martino, Lung Canc Unit, Genoa, Italy

[16] Careggi Univ Hosp, Dept Oncol, Florence, Italy

[17] Azienda Ospedal Univ, Osped Riuniti Foggia, Unita Oncol Med & Terapia Biomol, Foggia, Italy

[18] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[19] Sapienza Univ Rome, Policlin Umberto I, Med Oncol B, Rome, Italy

[20] Univ Hosp Santa Maria Misericordia, Dept Oncol, Udine, Italy

[21] Fermo Area Vasta 4, Med Oncol, Fermo, Italy

[22] Osped Riuniti Padova Sud Madre Teresa Calcutta, Med Oncol, Monselice, Italy

[23] Monaldi Hosp, Pneumooncol Unit, Naples, Italy

[24] IRCCS Osped Sacro Cuore Don Calabria, Oncol Unit, Negrar, Italy

[25] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy

[26] SS Annunziata Hosp, Clin Oncol Unit, Chieti, Italy

[27] F Spaziani Hosp, Med Oncol, Frosinone, Italy

[28] Santa Maria Goretti Hosp, Med Oncol, Latina, Italy

[29] Campus Bio Medico Univ, Med Oncol, Rome, Italy

[30] ASST Sette Laghi, Med Oncol, Varese, Italy

[31] Univ Hosp Parma, Med Oncol Unit, Parma, Italy

[32] AUSL Romagna, Dept Oncol & Hematol, Ravenna, Italy

[33] Univ Hosp Cagliari, Med Oncol Unit, Cagliari, Italy

[34] Univ Cagliari, Cagliari, Italy

[35] St Camillo Forlanini Hosp, Pneumooncol Unit, Rome, Italy

[36] Univ Turin, San Luigi Hosp, Dept Oncol, Orbassano, Italy

[37] Azienda Osped Perugia, Santa Maria Misericordia Hosp, Dept Med Oncol, Perugia, Italy

[38] Queen Alexandra Univ Hosp, Portsmouth Hosp NHS Trust, Oncol Dept, Portsmouth, Hants, England

[39] Univ Hosp Geneva, Oncol Dept, Geneva, Switzerland

来源：

THORACIC CANCER | 2021年 / 12卷 / 06期

关键词：

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

D O I：

10.1111/1759-7714.13852

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：880 / 889

页数：10

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