Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungenClinic Grosshansdorf, Grosshansdorf, Germany.
Department of Medical Oncology, Institutul Oncologic Prof. Dr. Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
J Thorac Oncol. 2023 Aug;18(8):1055-1069. doi: 10.1016/j.jtho.2023.04.021. Epub 2023 May 3.
In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years' minimum follow-up.
Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only).
Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months' minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43-0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66-0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed.
With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status.
在 CheckMate 227 第 1 部分中，nivolumab 联合 ipilimumab 延长了转移性 NSCLC 患者的总生存期（OS），与化疗相比，无论肿瘤程序性死亡配体 1（PD-L1）表达如何。在此，我们报告了在 5 年最小随访时根据基线脑转移状态进行的事后探索性系统和颅内疗效结果和安全性。
纳入未经治疗的 IV 期或复发性 NSCLC 患者，无 EGFR 或 ALK 改变，包括有治疗过的脑转移的无症状患者。肿瘤 PD-L1 大于或等于 1%的患者随机分为 nivolumab 联合 ipilimumab、nivolumab 或化疗组；肿瘤 PD-L1 小于 1%的患者随机分为 nivolumab 联合 ipilimumab、nivolumab 联合化疗或化疗组。评估包括 OS、盲法独立中央审查的系统和颅内无进展生存期、新脑病变发展和安全性。基线时进行脑成像（所有随机患者），此后每 12 周左右进行一次（仅基线有脑转移的患者）。
总体而言，1739 名随机患者中有 202 名基线时有脑转移（nivolumab 联合 ipilimumab：68；化疗：66）。在最小随访 61.3 个月时，与化疗相比，nivolumab 联合 ipilimumab延长了基线时有脑转移的患者的 OS（风险比=0.63；95%置信区间：0.43-0.92）和无脑转移的患者的 OS（风险比=0.76；95%置信区间：0.66-0.87）。基线时有脑转移的患者中，nivolumab 联合 ipilimumab 的 5 年系统和颅内无进展生存率更高（分别为 12%和 16%），化疗组分别为 0%和 6%。基线时有脑转移的患者中，nivolumab 联合 ipilimumab 组（4%）比化疗组（20%）发生新脑转移的患者更少。未观察到新的安全性信号。
所有患者停止免疫治疗超过或等于 3 年，nivolumab 联合 ipilimumab 继续为有或无脑转移的患者提供长期、持久的生存获益。颅内疗效结果有利于 nivolumab 联合 ipilimumab 与化疗相比。这些结果进一步支持 nivolumab 联合 ipilimumab 作为转移性 NSCLC 患者有效的一线治疗药物，无论基线脑转移状态如何。
