Peters Solange, Paz-Ares Luis G, Reck Martin, Carbone David P, Brahmer Julie R, Borghaei Hossein, Lu Shun, O'Byrne Kenneth J, John Thomas, Ciuleanu Tudor-Eliade, Schenker Michael, Bernabe Caro Reyes, Nishio Makoto, Cobo Manuel, Lee Jong-Seok, Zurawski Bogdan, Pluzanski Adam, Aoyama Takekazu, Tschaika Marina, Devas Vipul, Grootendorst Diederik J, Ramalingam Suresh S
Oncology Department, Lausanne University Hospital, Lausanne, Switzerland.
Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
J Thorac Oncol. 2025 Jan;20(1):94-108. doi: 10.1016/j.jtho.2024.09.1439. Epub 2024 Oct 4.
Nivolumab plus ipilimumab-based treatment regimens have shown long-term, durable efficacy benefits in patients with metastatic NSCLC. Here we report clinical outcomes from a pooled analysis of patients with metastatic NSCLC and tumor programmed death-ligand 1 (PD-L1) lower than 1% treated with first-line nivolumab plus ipilimumab with or without two cycles of chemotherapy versus up to four cycles of chemotherapy in the randomized phase 3 CheckMate 227 and CheckMate 9LA studies.
Patients were aged 18 years or older and had stage IV or recurrent NSCLC with no sensitizing EGFR/ALK alterations. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety.
In patients with tumor PD-L1 lower than 1% in the nivolumab plus ipilimumab with or without chemotherapy (n = 322) versus chemotherapy (n = 315) arms, median OS was 17.4 versus 11.3 months, respectively, (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.54-0.76; 5-y OS rate, 20% versus 7%) at a median follow-up of 73.7 months. The OS benefit was observed across key subgroups, including difficult-to-treat populations such as those with baseline brain metastases (HR = 0.44, 95% CI: 0.26-0.75) or squamous NSCLC (HR = 0.51, 95% CI: 0.36-0.72). In the overall pooled population, the median PFS was 5.4 versus 4.9 months (HR = 0.72, 95% CI: 0.60-0.87; 5-y PFS rate, 9% versus 2%), the objective response rate was 29% versus 22%, and the median duration of response was 18.0 versus 4.6 months. No new safety signals were observed.
Nivolumab plus ipilimumab with or without chemotherapy provides a long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 lower than 1%, supporting the use of this strategy as a first-line treatment option in this population with high unmet need.
NCT02477826, NCT03215706.
基于纳武利尤单抗加伊匹木单抗的治疗方案已在转移性非小细胞肺癌（NSCLC）患者中显示出长期、持久的疗效益处。在此，我们报告了在随机3期CheckMate 227和CheckMate 9LA研究中，对转移性NSCLC且肿瘤程序性死亡配体1（PD-L1）低于1%的患者进行汇总分析的临床结果，这些患者接受一线纳武利尤单抗加伊匹木单抗治疗，联合或不联合两个周期化疗，与接受多达四个周期化疗的情况进行对比。
患者年龄在18岁及以上，患有IV期或复发性NSCLC，且无敏感的表皮生长因子受体（EGFR）/间变性淋巴瘤激酶（ALK）改变。评估指标包括总生存期（OS）、无进展生存期（PFS）、客观缓解率、缓解持续时间和安全性。
在纳武利尤单抗加伊匹木单抗联合或不联合化疗组（n = 322）与化疗组（n = 315）中，肿瘤PD-L1低于1%的患者，中位OS分别为17.4个月和11.3个月（风险比[HR] = 0.64，95%置信区间[CI]：0.54 - 0.76；5年OS率分别为20%和7%），中位随访时间为73.7个月。在包括基线有脑转移（HR = 0.44，95% CI：0.26 - 0.75）或鳞状NSCLC（HR = 0.51，95% CI：0.36 - 0.72）等难以治疗的人群在内的关键亚组中均观察到OS获益。在总体汇总人群中，中位PFS分别为5.4个月和4.9个月（HR = 0.72，95% CI：0.60 - 0.87；5年PFS率分别为9%和2%），客观缓解率分别为29%和22%，中位缓解持续时间分别为18.0个月和4.6个月。未观察到新的安全信号。
纳武利尤单抗加伊匹木单抗联合或不联合化疗为转移性NSCLC且肿瘤PD-L1低于1%的患者提供了长期、持久的临床益处，支持将该策略作为这一有高度未满足需求人群的一线治疗选择。
NCT02477826，NCT03215706。
