Garassino Marina Chiara, Crinò Lucio, Catino Annamaria, Ardizzoni Andrea, Cortesi Enrico, Cappuzzo Federico, Bordi Paola, Calabrò Luana, Barbieri Fausto, Santo Antonio, Altavilla Giuseppe, Ambrosio Francesca, Mini Enrico, Vasile Enrico, Morgillo Floriana, Scoppola Alessandro, Bengala Carmelo, Follador Alessandro, Tedde Natale, Giannarelli Diana, Lo Russo Giuseppe, Vitiello Fabiana
1 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
2 Santa Maria della Misericordia Hospital, Perugia, Italy.
Tumour Biol. 2018 Nov;40(11):1010428318815047. doi: 10.1177/1010428318815047.
: Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer.
: Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored.
: Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7-20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2-9.6), respectively, in the overall expanded access program population. Any-grade and grade 3-4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3-4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall.
: Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.
从不吸烟者可能是晚期非小细胞肺癌患者中的一个独特亚组，似乎从免疫治疗中获益少于吸烟者。我们报告了参加意大利纳武利尤单抗扩大可及项目队列研究的经治晚期鳞状非小细胞肺癌从不吸烟者的结果。
应医生要求可使用纳武利尤单抗（每2周3mg/kg，持续≤24个月）。疗效数据包括客观肿瘤反应、进展日期和生存信息。对安全性进行监测。
总体而言，371例患者接受了至少一剂纳武利尤单抗，其中包括31例从不吸烟者（8%）。从不吸烟者的客观缓解率、疾病控制率和中位总生存期分别为23%、45%和12.1个月（95%置信区间：3.7 - 20.4），而在整个扩大可及项目人群中分别为18%、47%和7.9个月（95%置信区间：6.2 - 9.6）。在从不吸烟者中，分别有12例（39%）和3例（10%）报告了任何级别和3 - 4级治疗相关不良事件，在整个扩大可及项目人群中分别有109例（29%）和21例（6%）。非吸烟者中3 - 4级治疗相关不良事件为转氨酶升高（n = 2；6%）和腹泻（n = 1；3%）。治疗相关不良事件导致4例非吸烟者（17%）和26例患者（9%）总体停药。
在这个意大利扩大可及项目中，经治的晚期鳞状非小细胞肺癌从不吸烟者表现出的疗效和安全性与整个扩大可及项目人群及临床试验中的情况一致。这些结果表明，一部分鳞状非小细胞肺癌从不吸烟患者可能对免疫治疗有反应。其他因素，如肿瘤突变负荷以及程序性死亡配体1、间变性淋巴瘤激酶和表皮生长因子受体的状态，可能发挥潜在的关键作用。
