纳武单抗联合伊匹单抗一线治疗转移性NSCLC的安全性：CheckMate 227、568、817的汇总分析

SCI

17 September 2022

Safety of First-line Nivolumab Plus Ipilimumab in Patients With Metastatic Non-Small Cell Lung Cancer: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817

（J Thorac Oncol  IF:20.121）

• Paz-Ares LG, Ciuleanu T, Pluzanski A, Lee JS, Gainor JF, Otterson GA, Audigier-Valette C, Ready N, Schenker M, Linardou H, Caro RB, Provencio M, Zurawski B, Lee KH, Kim SW, Caserta C, Ramalingam SS, Spigel DR, Brahmer JR, Reck M, O'Byrne KJ, Girard N, Popat S, Peters S, Memaj A, Nathan F, Aanur N, Borghaei H. Safety of First-line Nivolumab Plus Ipilimumab in Patients With Metastatic Non-Small Cell Lung Cancer: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. J Thorac Oncol. 2022 Aug 29:S1556-0864(22)01556-8. doi: 10.1016/j.jtho.2022.08.014. Epub ahead of print. PMID: 36049658.

Introduction 引言

We characterized first-line nivolumab plus ipilimumab (NIVO+IPI) safety in a large patient population with metastatic non-small cell lung cancer (NSCLC) and efficacy outcomes after NIVO+IPI discontinuation due to treatment-related adverse events (TRAEs).

我们在大量转移性非小细胞肺癌 (NSCLC) 患者群体中描述了一线 nivolumab 加 ipilimumab (NIVO+IPI) 的安全性，以及因治疗相关不良事件 (TRAE) 而停用 NIVO+IPI 后的疗效结果.

Methods 方法

We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 weeks; IPI, 1 mg/kg every 6 weeks) in metastatic NSCLC (CheckMate 227 Part 1, CheckMate 817 cohort A, CheckMate 568 Part 1). Safety endpoints included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged ≥75 years.

我们汇总了转移性 NSCLC（CheckMate 227 第 1 部分，CheckMate 817 队列数据A，CheckMate 568 第 1 部分）中三项一线 NIVO+IPI 研究（NIVO，3 mg/kg 或 240 mg 每 2 周；IPI，1 mg/kg 每 6 周））。安全性终点包括汇总人群和 75 岁以上患者的 TRAE 和免疫介导的不良事件 (IMAE)。

Results 结果

 In the pooled population (N=1255), any-grade TRAEs occurred in 78% of patients, grade 3/4 TRAEs in 34%, and discontinuations of any regimen component due to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3/4, 2%) and rash (17%; grade 3/4, 3%), respectively. The most common grade 3/4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5/16). Safety in patients aged ≥75 years (n=174) was generally similar to the overall population, but discontinuations of any regimen component due to TRAEs were more common (29%). In patients discontinuing NIVO+IPI due to TRAEs (n=225), 3-year overall survival was 50% (95% CI: 42.6-56.0), and 42% (31.2-52.4) of 130 responders remained in response 2 years after discontinuation.

在汇总人群 (N=1255) 中，78% 的患者发生任何级别的 TRAE，34% 的患者发生 3/4 级 TRAE，21% 的患者因 TRAE 而中断任何治疗方案。最常见的 TRAE 和 IMAE 分别是腹泻（20%；3/4 级，2%）和皮疹（17%；3/4 级，3%）。最常见的 3/4 级 IMAE 是肝炎（5%）和腹泻/结肠炎和肺炎（各 4%）。肺炎是治疗相关死亡的最常见原因 (5/16)。≥75 岁患者 (n=174) 的安全性通常与总体人群相似，但因 TRAE 而终止任何方案成分的情况更为常见 (29%)。在因 TRAE（n=225）而停用 NIVO+IPI 的患者中，3 年总生存率为 50%（95% CI：42.6-56.0），130 名应答者中有 42%（31.2-52.4）在停用 2 年后仍保持应答。

Conclusions 结论

First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged ≥75 years. Discontinuations due to TRAEs did not reduce long-term survival.

一线 NIVO+IPI 在这一庞大的转移性 NSCLC 人群和年龄≥75 岁的患者中具有良好的耐受性。因 TRAE 导致的停药并未降低长期生存率。