Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients

被引：76

作者：

Garassino, Marina Chiara ^{[1
]}

Gelibter, Alain Jonathan ^{[2
]}

Grossi, Francesco ^{[3
]}

Chiari, Rita ^{[4
]}

Parra, Hector Soto ^{[5
]}

Cascinu, Stefano ^{[6
]}

Cognetti, Francesco ^{[7
]}

Turci, Daniele ^{[8
]}

Blasi, Livio ^{[9
]}

Bengala, Carmelo ^{[10
]}

Mini, Enrico ^{[11
]}

Baldini, Editta ^{[12
]}

Quadrini, Silvia ^{[13
]}

Ceresoli, Giovanni Luca ^{[14
]}

Antonelli, Paola ^{[15
]}

Vasile, Enrico ^{[16
]}

Pinto, Carmine ^{[17
]}

Fasola, Gianpiero ^{[18
]}

Galetta, Domenico ^{[19
]}

Macerelli, Marianna ^{[18
]}

Giannarelli, Diana ^{[7
]}

Lo Russo, Giuseppe ^{[1
]}

de Marinis, Filippo ^{[20
]}

机构：

[1] Natl Canc Inst, Med Oncol Dept, Thorac Oncol Unit, 1 Venezian St, I-20133 Milan, Italy

[2] Sapienza Univ Rome, Umberto Hosp 1, Oncol Unit, Rome, Italy

[3] San Martino Hosp, Lung Canc Unit, Genoa, Italy

[4] Univ Perugia, Dept Engn, Perugia, Italy

[5] Vittorio Emanuele Hosp, Dept Oncol, Catania, Italy

[6] Univ Modena & Reggio Emilia, Dept Oncol Haematol, Modena, Italy

[7] Regina Elena Inst Canc Res, Dept Oncol, Rome, Italy

[8] Santa Maria Croci Hosp, Dept Oncol, Ravenna, Italy

[9] Palermo Hosp, Dept Oncol, Palermo, Italy

[10] Misericordia Hosp, Oncol Dept, Grosseto, Italy

[11] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[12] Lucca Hosp, Dept Oncol, Lucca, Italy

[13] Santissima Trinita Hosp, Dept Oncol, Sora, Frosinone, Italy

[14] Humanitas Gavezzeni Hosp, Dept Med Oncol, Bergamo, Italy

[15] Busto Arsizio Hosp, Dept Oncol, Varese, Italy

[16] Univ Hosp Pisa, Dept Oncol, Polo Oncol, Pisa, Italy

[17] Santa Maria Nuova Hosp, Clin Canc Ctr, Med Oncol Unit, Reggio Emilia, Italy

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

[19] Clin Canc Ctr Giovanni Paolo II, Med Oncol Unit, Bari, Italy

[20] European Inst Oncol, Div Thorac Oncol, Milan, Italy

来源：

JOURNAL OF THORACIC ONCOLOGY | 2018年 / 13卷 / 08期

关键词：

Nonsquamous non-small cell lung cancer; Expanded access program; nivolumab; EGFR positive; Never-smokers; RANDOMIZED CONTROLLED-TRIAL; 1ST-LINE TREATMENT; OPEN-LABEL; DOUBLET CHEMOTHERAPY; DOCETAXEL; ATEZOLIZUMAB; METAANALYSIS; MULTICENTER; PROGRESSION; THERAPY;

D O I：

10.1016/j.jtho.2018.04.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：1146 / 1155

页数：10

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