Paz-Ares Luis G, Ciuleanu Tudor-Eliade, Pluzanski Adam, Lee Jong-Seok, Gainor Justin F, Otterson Gregory A, Audigier-Valette Clarisse, Ready Neal, Schenker Michael, Linardou Helena, Caro Reyes Bernabe, Provencio Mariano, Zurawski Bogdan, Lee Ki Hyeong, Kim Sang-We, Caserta Claudia, Ramalingam Suresh S, Spigel David R, Brahmer Julie R, Reck Martin, O'Byrne Kenneth J, Girard Nicolas, Popat Sanjay, Peters Solange, Memaj Arteid, Nathan Faith, Aanur Nivedita, Borghaei Hossein
Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
Department of Medical Oncology, Institutul Oncologic Prof. Dr. Ion Chiricuta and University of Medicine and Pharmacy Iulia Hatieganu, Cluj-Napoca, Romania.
J Thorac Oncol. 2023 Jan;18(1):79-92. doi: 10.1016/j.jtho.2022.08.014. Epub 2022 Aug 30.
We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).
We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 wk; IPI, 1 mg/kg every 6 wk) in metastatic NSCLC (CheckMate 227 part 1, CheckMate 817 cohort A, CheckMate 568 part 1). Safety end points included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged 75 years or older.
In the pooled population (N = 1255), any-grade TRAEs occurred in 78% of the patients, grade 3 or 4 TRAEs in 34%, and discontinuation of any regimen component owing to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3 or 4, 2%) and rash (17%; grade 3 or 4, 3%), respectively. The most common grade 3 or 4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5 of 16). Safety in patients aged 75 years or older (n = 174) was generally similar to the overall population, but discontinuation of any regimen component owing to TRAEs was more common (29%). In patients discontinuing NIVO+IPI owing to TRAEs (n = 225), 3-year overall survival was 50% (95% confidence interval: 42.6-56.0), and 42% (31.2-52.4) of 130 responders remained in response 2 years after discontinuation.
First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged 75 years or older. Discontinuation owing to TRAEs did not reduce long-term survival.
我们在大量转移性非小细胞肺癌（NSCLC）患者群体中，对一线纳武利尤单抗联合伊匹木单抗（NIVO+IPI）的安全性，以及因治疗相关不良事件（TRAEs）停用NIVO+IPI后的疗效结果进行了特征分析。
我们汇总了三项一线NIVO+IPI治疗转移性NSCLC研究（CheckMate 227第1部分、CheckMate 817队列A、CheckMate 568第1部分）的数据（NIVO，3mg/kg或每2周240mg；IPI，每6周1mg/kg）。安全性终点包括汇总人群以及75岁及以上患者中的TRAEs和免疫介导的不良事件（IMAEs）。
在汇总人群（N = 1255）中，78%的患者发生了任何级别的TRAEs，34%的患者发生了3级或4级TRAEs，21%的患者因TRAEs停用了任何方案组分。最常见的TRAEs和IMAEs分别是腹泻（20%；3级或4级，2%）和皮疹（17%；3级或4级，3%）。最常见的3级或4级IMAEs是肝炎（5%）以及腹泻/结肠炎和肺炎（各4%）。肺炎是治疗相关死亡的最常见原因（16例中有5例）。75岁及以上患者（n = 174）的安全性总体上与总体人群相似，但因TRAEs停用任何方案组分的情况更常见（29%）。在因TRAEs停用NIVO+IPI的患者（n = 225）中，3年总生存率为50%（95%置信区间：42.6 - 56.0），130例缓解者中有42%（31.2 - 52.4）在停药2年后仍处于缓解状态。
在这个大量转移性NSCLC患者群体以及75岁及以上患者中，一线NIVO+IPI耐受性良好。因TRAEs停药并未降低长期生存率。
