Borghaei H, Ciuleanu T-E, Lee J-S, Pluzanski A, Caro R Bernabe, Gutierrez M, Ohe Y, Nishio M, Goldman J, Ready N, Spigel D R, Ramalingam S S, Paz-Ares L G, Gainor J F, Ahmed S, Reck M, Maio M, O'Byrne K J, Memaj A, Nathan F, Tran P, Hellmann M D, Brahmer J R
Hematology and Oncology Department, Fox Chase Cancer Center, Philadelphia, USA.
Department of Medical Oncology, Institutul Oncologic Prof Dr Ion Chiricuta, Cluj-Napoca; Department of Medical Oncology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
Ann Oncol. 2023 Feb;34(2):173-185. doi: 10.1016/j.annonc.2022.11.006. Epub 2022 Nov 19.
First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed.
In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population.
Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.
在晚期非小细胞肺癌（NSCLC）中，一线纳武利尤单抗联合伊匹木单抗相较于化疗可延长生存期。我们在一个大型汇总患者群体中进一步明确了该方案的临床获益，并评估了缓解对生存的影响。
数据来自四项关于一线纳武利尤单抗联合伊匹木单抗治疗晚期NSCLC的研究（CheckMate 227第1部分、817队列A、568第1部分和012）。评估了总生存期（OS）、无进展生存期（PFS）、客观缓解率、缓解持续时间和安全性。还评估了根据6个月时的缓解状态以及纳武利尤单抗联合伊匹木单抗治疗缓解者的肿瘤负荷降低情况对OS进行的标志性分析。
在汇总人群（N = 1332）中，最短随访时间为29.1 - 58.9个月，中位OS为18.6个月，3年OS率为35%；中位PFS为5.4个月（3年PFS率为17%）。客观缓解率为36%；中位缓解持续时间为23.7个月，38%的缓解者在3年时仍持续缓解。在肿瘤程序性死亡配体1（PD-L1）<1%、≥1%、1% - 49%或≥50%的患者中，3年OS率分别为30%、38%、30%和48%。鳞状或非鳞状组织学类型的患者3年OS率分别为30%和38%。≥75岁患者的疗效结果与总体汇总人群相似（中位OS，20.1个月；3年OS率，34%）。在汇总人群中，6个月时对纳武利尤单抗联合伊匹木单抗有反应者的标志性后OS长于病情稳定或进展的患者；3年OS率分别为66%、22%和14%。缓解深度越大，生存期越长；在肿瘤负荷降低≥80%、50%至<80%或30%至<50%的患者中，3年OS率分别为85%、72%和44%。在汇总人群中未发现新的安全信号。
在这个大型患者群体中，纳武利尤单抗联合伊匹木单抗具有长期生存获益和持久缓解，进一步支持了其作为晚期NSCLC的一线治疗选择。
